Jack Rosenbluth, M.D.

A novel path for rapid transverse communication of vestibular signals in turtle cerebellum
Brown, Michael E; Martin, John R; Rosenbluth, Jack; Ariel, Michael
2011 Mar;105(3):1071-1088, Journal of neurophysiology
Voltage-sensitive dye activity within the thin, unfoliated turtle cerebellar cortex (Cb) was recorded in vitro during eighth cranial nerve (nVIII) stimulation. Short latency responses were localized to the middle of the lateral edges of both ipsilateral and contralateral Cb [vestibulocerebellum (vCb)]. Even with a severed contralateral Cb peduncle, stimulation of the nVIII ipsilateral to the intact peduncle evoked contralateral vCb responses with a mean latency of only 0.25 ms after the ipsilateral responses, even though the distance between them was approximately 5 mm. We investigated whether a rapidly conducting commissure exists between each vCb by stimulating one of them directly. Responses in both vCb spread sagittally, but, surprisingly, there was no sequential activation along a transverse Cb beam between them. In contrast, stimulation medial to either vCb evoked transverse beams that required approximately 20 ms to cross the Cb. Therefore, the rapid commissural connection between each vCb is not mediated by slowly conducting parallel fibers. Also, the vCb was not strongly activated by climbing fiber stimulation, suggesting that inputs to vCb involve distinct cerebellar circuits. Responses between the two vCb remained following knife cuts through the rostral and caudal Cb along the midline, through both peduncles, and even shallow midline cuts to the middle Cb through its white matter and granule cell layer. Commissural responses were still observed only with a narrow transverse bridge between each vCb or in thick transverse Cb slices. Horseradish peroxidase transport from one vCb labeled transverse axons traveling within the Purkinje cell layer that were larger than parallel fibers and lacked varicosities. In sagittal sections, cross-section profiles of myelinated axons were observed around Purkinje cells midway between the rostral and caudal Cb. This novel pathway for transverse communication between lateral edges of turtle Cb suggests that afferents may directly conduct vestibular information rapidly across the Cb to coordinate vestibulomotor reflex behaviors
— id: 134254, year: 2011, vol: 105, page: 1071, stat: Journal Article,

Paranodal permeability in "myelin mutants"
Shroff, Seema; Mierzwa, Amanda; Scherer, Steven S; Peles, Elior; Arevalo, Juan C; Chao, Moses V; Rosenbluth, Jack
2011 Oct;59(10):1447-1457, Glia
Fluorescent dextran tracers of varying sizes have been used to assess paranodal permeability in myelinated sciatic nerve fibers from control and three 'myelin mutant' mice, Caspr-null, cst-null, and shaking. We demonstrate that in all of these the paranode is permeable to small tracers (3 kDa and 10 kDa), which penetrate most fibers, and to larger tracers (40 kDa and 70 kDa), which penetrate far fewer fibers and move shorter distances over longer periods of time. Despite gross diminution in transverse bands (TBs) in the Caspr-null and cst-null mice, the permeability of their paranodal junctions is equivalent to that in controls. Thus, deficiency of TBs in these mutants does not increase the permeability of their paranodal junctions to the dextrans we used, moving from the perinodal space through the paranode to the internodal periaxonal space. In addition, we show that the shaking mice, which have thinner myelin and shorter paranodes, show increased permeability to the same tracers despite the presence of TBs. We conclude that the extent of penetration of these tracers does not depend on the presence or absence of TBs but does depend on the length of the paranode and, in turn, on the length of 'pathway 3,' the helical extracellular pathway that passes through the paranode parallel to the lateral edge of the myelin sheath. (c) 2011 Wiley-Liss, Inc
— id: 135571, year: 2011, vol: 59, page: 1447, stat: Journal Article,

Myelin protein composition is altered in mice lacking either sulfated or both sulfated and non-sulfated galactolipids
Fewou, Simon Ngamli; Fernandes, Alda; Stockdale, Katie; Francone, Victor P; Dupree, Jeffrey L; Rosenbluth, Jack; Pfeiffer, Steven E; Bansal, Rashmi
2010 Feb;112(3):599-610, Journal of neurochemistry
Myelin is highly enriched in galactocerebroside (GalCer) and its sulfated form sulfatide. Mice, unable to synthesize GalCer and sulfatide (CGT(null)) or sulfatide alone (CST(null)), exhibit disorganized paranodal structures and progressive dysmyelination. To obtain insights into the molecular mechanisms underlying these defects, we examined myelin composition of these mutants by two-dimensional differential fluorescence intensity gel electrophoresis proteomic approach and immunoblotting. We identified several proteins whose expressions were significantly altered in these mutants. These proteins are known to regulate cytoskeletal dynamics, energy metabolism, vesicular trafficking or adhesion, suggesting a disruption in these physiological processes in the absence of myelin galactolipids. Further analysis of one of these proteins, nucleotide diphosphate kinase (NDK)/Nm23, showed that it was reduced in myelin of CGT(null) and increased in CST(null), but not in whole brain homogenate. Immunostaining showed an increase in its expression in the cell bodies of CGT(null)- and a decrease in CST(null)-oligodenrocytes, together leading to the hypothesis that transport of NDK/Nm23 from oligodenrocyte cell bodies into myelin may be differentially dysregulated in the absence of these galactolipids. This study provides new insights into the changes that occur in the composition/distribution of myelin proteins in mice lacking either unsulfated and/or sulfated galactolipids and reinforces the role of these lipids in intracellular trafficking
— id: 134970, year: 2010, vol: 112, page: 599, stat: Journal Article,

Role of transverse bands in maintaining paranodal structure and axolemmal domain organization in myelinated nerve fibers: Effect on longevity in dysmyelinated mutant mice
Mierzwa, Amanda J; Arevalo, Juan-Carlos; Schiff, Rolf; Chao, Moses V; Rosenbluth, Jack
2010 Jul 15;518(14):2841-2853, Journal of comparative neurology
The consequences of dysmyelination are poorly understood and vary widely in severity. The shaking mouse, a quaking allele, is characterized by severe central nervous system (CNS) dysmyelination and demyelination, a conspicuous action tremor, and seizures in approximately 25% of animals, but with normal muscle strength and a normal lifespan. In this study we compare this mutant with other dysmyelinated mutants including the ceramide sulfotransferase deficient (CST-/-) mouse, which are more severely affected behaviorally, to determine what might underlie the differences between them with respect to behavior and longevity. Examination of the paranodal junctional region of CNS myelinated fibers shows that 'transverse bands,' a component of the junction, are present in nearly all shaking paranodes but in only a minority of CST-/- paranodes. The number of terminal loops that have transverse bands within a paranode and the number of transverse bands per unit length are only moderately reduced in the shaking mutant, compared with controls, but markedly reduced in CST-/- mice. Immunofluorescence studies also show that although the nodes of the shaking mutant are somewhat longer than normal, Na(+) and K(+) channels remain separated, distinguishing this mutant from CST-/- mice and others that lack transverse bands. We conclude that the essential difference between the shaking mutant and others more severely affected is the presence of transverse bands, which serve to stabilize paranodal structure over time as well as the organization of the axolemmal domains, and that differences in the prevalence of transverse bands underlie the marked differences in progressive neurological impairment and longevity among dysmyelinated mouse mutants. J. Comp. Neurol. 518:2841-2853, 2010. (c) 2010 Wiley-Liss, Inc
— id: 109814, year: 2010, vol: 518, page: 2841, stat: Journal Article,

Permeability of the paranodal junction of myelinated nerve fibers
Mierzwa, Amanda; Shroff, Seema; Rosenbluth, Jack
2010 Nov 24;30(47):15962-15968, Journal of neuroscience
We have used fluorescent dextran tracers to test the tightness of the paranodal junction of living or fixed myelinated fibers in mouse sciatic nerve. Both 3 and 70 kDa tracers are able to penetrate from the perinodal space symmetrically into the paranodes on either side of the node of Ranvier at a rate consistent with diffusion through an elongated helical pathway between the paranodal terminal loops of the myelin sheath. This pathway thus provides an access route for movement of water soluble nutrients and metabolites to and from the internodal axon and constitutes a pathway through which juxtaparanodal potassium channels may be activated and may in turn affect nodal excitability. This pathway may also allow access of antibodies and toxic molecules to the internodal axon in paraneoplastic syndromes and demyelinating diseases
— id: 114849, year: 2010, vol: 30, page: 15962, stat: Journal Article,

The ultrastructure and contractile properties of a fast-acting, obliquely striated, myosin-regulated muscle: the funnel retractor of squids
Rosenbluth, Jack; Szent-Gyorgyi, Andrew G; Thompson, Joseph T
2010 Jul 15;213(Pt 14):2430-2443, Journal of experimental biology
We investigated the ultrastructure, contractile properties, and in vivo length changes of the fast-acting funnel retractor muscle of the long-finned squid Doryteuthis pealeii. This muscle is composed of obliquely striated, spindle-shaped fibers ~3 mum across that have an abundant sarcoplasmic reticulum, consisting primarily of membranous sacs that form 'dyads' along the surface of each cell. The contractile apparatus consists of 'myofibrils' approximately 0.25-0.5 microm wide in cross section arrayed around the periphery of each cell, surrounding a central core that contains the nucleus and large mitochondria. Thick myofilaments are approximately 25 nm in diameter and approximately 2.8 microm long. 'Dense bodies' are narrow, resembling Z lines, but are discontinuous and are not associated with the cytoskeletal fibrillar elements that are so prominent in slower obliquely striated muscles. The cells approximate each other closely with minimal intervening intercellular connective tissue. Our physiological experiments, conducted at 17 degrees C, showed that the longitudinal muscle fibers of the funnel retractor were activated rapidly (8 ms latent period following stimulation) and generated force rapidly (peak twitch force occurred within 50 ms). The longitudinal fibers had low V(max) (2.15 +/-0.26 L(0) s(-1), where L(0) was the length that generated peak isometric force) but generated relatively high isometric stress (270+/-20 mN mm(-2) physiological cross section). The fibers exhibited a moderate maximum power output (49.9 W kg(-1)), compared with vertebrate and arthropod cross striated fibers, at a V/V(max) of 0.33+/-0.044. During ventilation of the mantle cavity and locomotion, the funnel retractor muscle operated in vivo over a limited range of strains (+0.075 to -0.15 relative to resting length, L(R)) and at low strain rates (from 0.16 to 0.91 L(R) s(-1) ), corresponding to a range of V/V(max) from 0.073 to 0.42. During the exhalant phase of the jet the range of strains was even narrower: maximum range less than +/-0.04, with the muscle operating nearly isometrically during ventilation and slow, arms-first swimming. The limited length operating range of the funnel retractor muscles, especially during ventilation and slow jetting, suggests that they may act as muscular struts
— id: 134341, year: 2010, vol: 213, page: 2430, stat: Journal Article,

Spinal cord dysmyelination caused by an antiproteolipid protein IgM antibody: implications for the mechanism of central nervous system myelin formation
Rosenbluth, J; Schiff, R
2009 Mar;87(4):956-963, Journal of neuroscience research
Antiglycolipid IgM antibodies are known to induce formation of 'wide spaced' or 'expanded' myelin, a distinctive form of dysmyelination characterized by a repeat period approximately two or three times normal, which is seen also in diseases, including multiple sclerosis. To determine whether an antibody directed against a myelin protein would cause equivalent pathology, we implanted O10 hybridoma cells into the spinal cord of adult or juvenile rats. O10 produces an IgM directed against PLP, the major protein of CNS myelin. Subsequent examination of the cords showed focal demyelination and remyelination. In addition, however, some juvenile cords, but none of the adult cords, displayed wide-spaced myelin with lamellae separated by an extracellular material comprising elements consistent with IgM molecules in appearance. Wide spacing tended to involve the outer layers of the sheath and in some cases alternated with normally spaced lamellae. A feature not seen previously consists of multiple expanded myelin lamellae in one sector of a sheath continuous with normally spaced lamellae in another, resulting in variation in sheath thickness around the axonal circumference. This uneven distribution of wide-spaced lamellae is most simply explained based on incorporation of IgM molecules into immature sheaths during myelin formation and implies a model of CNS myelinogenesis more complex than simple spiraling. The periaxonal space never displays widening of this kind, but the interface with adjacent myelin sheaths or oligodendrocytes may. Thus, wide spacing appears to require that IgM molecules bridge between two PLP-containing membranes and does not reflect the mere presence of immunoglobulin within the extracellular space
— id: 97780, year: 2009, vol: 87, page: 956, stat: Journal Article,

Multiple functions of the paranodal junction of myelinated nerve fibers
Rosenbluth, Jack
2009 Nov 15;87(15):3250-3258, Journal of neuroscience research
Myelin sheaths include an extraordinary structure, the 'paranodal axoglial junction' (PNJ), which attaches the sheath to the axon at each end of each myelin segment. Its size is enormous and its structure unique. Here we review past and current studies showing that this junction can serve multiple functions in maintaining reliable saltatory conduction. The present evidence points to three functions in particular. 1) It seals the myelin sheath to the axon to prevent major shunting of nodal action currents beneath the myelin sheath while still leaving a narrow channel interconnecting the internodal periaxonal space with the perinodal space. This pathway represents a potential route through which juxtaparanodal and internodal channels can influence nodal activity and through which nutrients, such as glucose, and other metabolites can diffuse to and from the internodal periaxonal space. 2) It serves as a mechanism for maintaining discrete, differentiated axolemmal domains at and around the node of Ranvier by acting as a barrier to the lateral movement of ion channel complexes within the axolemma, thus concentrating voltage-gated sodium channels at the node and segregating fast voltage-gated potassium channels to the juxtaparanode under the myelin sheath. 3) It attaches the myelin sheath to the axon on either side of the node and can thus maintain nodal dimensions in the face of mechanical stresses associated with stretch or other local factors that might cause disjunction. It is therefore the likely means for maintaining constancy of nodal surface area and electrical parameters essential for consistency in conduction. (c) 2009 Wiley-Liss, Inc
— id: 94511, year: 2009, vol: 87, page: 3250, stat: Journal Article,

Effects of osmolality on PLP-null myelin structure: implications re axon damage
Rosenbluth, Jack; Schiff, Rolf; Lam, Pokman
2009 Feb 9;1253:191-197, Brain research
In order to test the adhesiveness of PLP-null compact myelin lamellae we soaked aldehyde-fixed CNS specimens from PLP-null and control mice overnight in distilled water, in Ringer's solution or in Ringer's solution with added 1 M sucrose. Subsequent examination of the tissue by EM showed that both PLP-null and control white matter soaked in Ringer remained largely compact. After the distilled water soak, control myelin was virtually unchanged, but PLP-null myelin showed some decompaction, i.e., separation of myelin lamellae from one another. After the sucrose/Ringer soak, normal myelin developed foci of decompaction, but the great majority of lamellae remained compact. In the PLP-null specimens, in contrast, many of the myelin sheaths became almost completely decompacted. Such sheaths became thicker overall and were comprised of lamellae widely separated from one another by irregular spaces. Thus, in normal animals, fixed CNS myelin lamellae are firmly adherent and resist separation; PLP-null myelin lamellae, in contrast, are poorly adherent and more readily separated. Mechanisms by which impaired adhesiveness of PLP-null myelin lamellae and fluctuations in osmolality in vivo might underlie slowing of conduction and axon damage are discussed
— id: 94512, year: 2009, vol: 1253, page: 191, stat: Journal Article,

Spongiform pathology in mouse CNS lacking 'neuropathy target esterase' and cellular prion protein
Rosenbluth, Jack; Schiff, Rolf; Lam, Pokman; Nuriel, Tal; Chao, Moses V
2009 Sep;35(3):433-437, Neurobiology of disease
Conditional inactivation of the 'neuropathy target esterase' (NTE) gene in mouse nerve cells was previously shown to result in CNS pathology comparable to the spongiform encephalopathy characteristic of prion diseases. To determine whether cellular prion protein (PrPc) is essential for development of this pathology we examined hippocampi of mice lacking NTE alone, PrPc alone or both NTE and PrPc. Light microscopic survey showed clear-cut spongiform changes in a majority of NTE-/- and NTE/PrP-/- double knockout mice but in only one PrP-/- mouse. EM analysis of spongiform lesions from NTE-/- and NTE/PrP-/- mice, and from the one affected PrP-/- mouse, revealed patches of branching tubular inclusions, comparable to the 'tubulovesicular inclusions' described previously in prion diseases. We conclude that spongiform pathology in conditional NTE knockout mice is not mediated by PrPc, and that tubulovesicular inclusions can be seen in spongiform encephalopathy of other etiologies and are not pathognomonic of prion disease
— id: 101443, year: 2009, vol: 35, page: 433, stat: Journal Article,

The potential of marrow stromal cells to differentiate into CNS myelin
Campbell, Kirk A; Schiff, Rolf; Rosenbluth, Jack
2007 ;1:36-36, Probe: the publication of research on biomedical endeavors
— id: 75327, year: 2007, vol: 1, page: 36, stat: Journal Article,

Mice with conditional inactivation of fibroblast growth factor receptor-2 signaling in oligodendrocytes have normal myelin but display dramatic hyperactivity when combined with Cnp1 inactivation
Kaga, Y; Shoemaker, WJ; Furusho, M; Bryant, M; Rosenbluth, J; Pfeiffer, SE; Oh, L; Rasband, M; Lappe-Siefke, C; Yu, K; Ornitz, DM; Nave, KA; Bansal, R
2006 NOV 22 ;26(47):12339-12350, Journal of neuroscience
Fibroblast growth factor receptors (Fgfr) comprise a widely expressed family of developmental regulators implicated in oligodendrocyte (OL) maturation of the CNS. Fgfr2 is expressed by OLs in myelinated fiber tracks. In vitro, Fgfr2 is highly upregulated during OL terminal differentiation, and its activation leads to enhanced growth of OL processes and the formation of myelin-like membranes. To investigate the in vivo function of Fgfr2 signaling by myelinating glial cells, we inactivated the floxed Fgfr2 gene in mice that coexpress Cre recombinase (cre) as a knock-in gene into the OL-specific 2 ',3 '-cyclic nucleotide phosphodiesterase (Cnp 1) locus. Surprisingly, no obvious defects were detected in brain development of these conditional mutants, including the number of OLs, the onset and extent of myelination, the ultrastructure of myelin, and the expression level of myelin proteins. However, unexpectedly, a subset of these conditional Fgfr2 knock-out mice that are homozygous for cre and therefore are also Cnp 1 null, displayed a dramatic hyperactive behavior starting at similar to 2 weeks of age. This hyperactivity was abolished by treatment with dopamine receptor antagonists or catecholamine biosynthesis inhibitors, suggesting that the symptoms involve a dysregulation of the dopaminergic system. Although the molecular mechanisms are presently unknown, this novel mouse model of hyperactivity demonstrates the potential involvement of OLs in neuropsychiatric disorders, as well as the nonpredictable role of genetic interactions in the behavioral phenotype of mice
— id: 69451, year: 2006, vol: 26, page: 12339, stat: Journal Article,

Sulfatide is essential for the maintenance of CNS myelin and axon structure
Marcus, J; Honigbaum, S; Shroff, S; Honke, K; Rosenbluth, J; Dupree, JL
2006 MAR ;53(4):372-381, Glia
Galactocerebroside (Ga1C) and sulfatide are abundant myelin lipids. In mice incapable of synthesizing these lipids, myelin is thin and regionally unstable and exhibits several subtle structural abnormalities. Although galactolipid-null mice have been beneficial in the analysis of galactolipid function, it has not been possible to differentiate between the functions of GalC and sulfatide with these mice alone. In the present work, we have analyzed a murine model that forms normal levels of Ga1C but is incapable of synthesizing sulfatide. By comparing a plethora of morphological features between the galactolipid-null and the sulfatide-null mice, we have begun to differentiate between the specific functions of these closely related lipids. The most striking difference between these two mutants is the reduction of myelin developmental abnormalities (e.g., redundant and uncompacted myelin sheaths) in young adult sulfatide-null mice as compared with the galactolipid-null animals. Although sulfatide appears to play a limited role in myelin development, this lipid is essential for myelin maintenance, as the prevalence of redundant, uncompacted, and degenerating myelin sheaths as well as deteriorating nodal/paranodal structure is increased significantly in aged sulfatide-null mice as compared with litter-mate wildtype mice. Finally, we show that the role played by sulfatide in CNS maintenance is not limited to the myelin sheath, as axonal caliber and circularity are normal in young adult mutant mice but are significantly altered in aged sulfatide-null animals. (c) 2005 Wiley-Liss, Inc
— id: 62833, year: 2006, vol: 53, page: 372, stat: Journal Article,

Subtle myelin defects in PLP-null mice
Rosenbluth, Jack; Nave, Klaus-Armin; Mierzwa, Amanda; Schiff, Rolf
2006 Aug 15;54(3):172-182, Glia
This study explores subtle defects in the myelin of proteolipid protein (PLP)-null mice that could potentially underlie the functional losses and axon damage known to occur in this mutant and in myelin diseases including multiple sclerosis. We have compared PLP-null central nervous system (CNS) myelin with normal myelin using ultrastructural methods designed to emphasize fine differences. In the PLP-null CNS, axons large enough to be myelinated often lack myelin entirely or are surrounded by abnormally thin sheaths. Short stretches of cytoplasm persist in many myelin lamellae. Most strikingly, compaction is incomplete in this mutant as shown by the widespread presence of patent interlamellar spaces of variable width that can be labeled with ferricyanide, acting as an aqueous extracellular tracer. In thinly myelinated fibers, interlamellar spaces are filled across the full width of the sheaths. In thick myelin sheaths, they appear filled irregularly but diffusely. These patent spaces constitute a spiral pathway through which ions and other extracellular agents may penetrate gradually, possibly contributing to the axon damage known to occur in this mutant, especially in thinly myelinated fibers, where the spiral path length is shortest and most consistently labeled. We show also that the 'radial component' of myelin is distorted in the mutant ('diagonal component'), extending across the sheaths at 45 degrees instead of 90 degrees. These observations indicate a direct or indirect role for PLP in maintaining myelin compaction along the external surfaces of the lamellae and to a limited extent, along the cytoplasmic surfaces as well and also in maintaining the normal alignment of the radial component
— id: 68750, year: 2006, vol: 54, page: 172, stat: Journal Article,

Neuregulin-1 type III determines the ensheathment fate of axons
Taveggia, Carla; Zanazzi, George; Petrylak, Ashley; Yano, Hiroko; Rosenbluth, Jack; Einheber, Steven; Xu, Xiaorong; Esper, Raymond M; Loeb, Jeffrey A; Shrager, Peter; Chao, Moses V; Falls, Douglas L; Role, Lorna; Salzer, James L
2005 Sep 1;47(5):681-694, Neuron
The signals that determine whether axons are ensheathed or myelinated by Schwann cells have long been elusive. We now report that threshold levels of neuregulin-1 (NRG1) type III on axons determine their ensheathment fate. Ensheathed axons express low levels whereas myelinated fibers express high levels of NRG1 type III. Sensory neurons from NRG1 type III deficient mice are poorly ensheathed and fail to myelinate; lentiviral-mediated expression of NRG1 type III rescues these defects. Expression also converts the normally unmyelinated axons of sympathetic neurons to myelination. Nerve fibers of mice haploinsufficient for NRG1 type III are disproportionately unmyelinated, aberrantly ensheathed, and hypomyelinated, with reduced conduction velocities. Type III is the sole NRG1 isoform retained at the axon surface and activates PI 3-kinase, which is required for Schwann cell myelination. These results indicate that levels of NRG1 type III, independent of axon diameter, provide a key instructive signal that determines the ensheathment fate of axons
— id: 58738, year: 2005, vol: 47, page: 681, stat: Journal Article,

Brain-specific deletion of neuropathy target esterase/swisscheese results in neurodegeneration
Akassoglou, Katerina; Malester, Brian; Xu, Jixiang; Tessarollo, Lino; Rosenbluth, Jack; Chao, Moses V
2004 May 6;101(14):5075-5080, Proceedings of the National Academy of Sciences of the United States of America
Neuropathy target esterase (NTE) is a neuronal membrane protein originally identified for its property to be modified by organo-phosphates (OPs), which in humans cause neuropathy characterized by axonal degeneration. Drosophila mutants for the homolog gene of NTE, swisscheese (sws), indicated a possible involvement of sws in the regulation of axon-glial cell interaction during glial wrapping. However, the role of NTE/sws in mammalian brain pathophysiology remains unknown. To investigate NTE function in vivo, we used the cre/loxP site-specific recombination strategy to generate mice with a specific deletion of NTE in neuronal tissues. Here we show that loss of NTE leads to prominent neuronal pathology in the hippocampus and thalamus and also defects in the cerebellum. Absence of NTE resulted in disruption of the endoplasmic reticulum, vacuolation of nerve cell bodies, and abnormal reticular aggregates. Thus, these results identify a physiological role for NTE in the nervous system and indicate that a loss-of-function mechanism may contribute to neurodegenerative diseases characterized by vacuolation and neuronal loss
— id: 46188, year: 2004, vol: 101, page: 5075, stat: Journal Article,

Sanford Louis Palay (23 September 1918 - 5 August 2002)
Peters, Alan; Rosenbluth, Jack; Pappas, George D; Kruger, Lawrence; Mugnaini, Enrico
2004 Dec;148(4):519-528, Proceedings of the American Philosophical Society
— id: 94513, year: 2004, vol: 148, page: 519, stat: Journal Article,

Sanford Louis Palay
Peters, Alan; Rosenbluth, Jack; Pappas, George; Kruger, Lawrence; Mugnaini, Enrico
2004 ;84:270-284, Biographical memoirs (National Academy of Sciences)
— id: 94514, year: 2004, vol: 84, page: 270, stat: Journal Article,

Role of myelination in the development of a uniform olivocerebellar conduction time
Lang, Eric J; Rosenbluth, Jack
2003 Apr;89(4):2259-2270, Journal of neurophysiology
Purkinje cells generate simultaneous complex spikes as a result of olivocerebellar activity. This synchronization (to within 1 ms) is thought to result from electrotonic coupling of inferior olivary neurons. However, the distance from the inferior olive (IO) varies across the cerebellar cortex. Thus signals generated simultaneously at the IO should arrive asynchronously across the cerebellar cortex, unless the length differences are compensated for. Previously, it was shown that the conduction time from the IO to the cerebellar cortex remains nearly constant at approximately 4 ms in the rat, implying the existence of such compensatory mechanisms. Here, we examined the role of myelination in generating a constant olivocerebellar conduction time by investigating the latency of complex spikes evoked by IO stimulation during development in normal rats and myelin-deficient mutants. In normal rats, myelination not only reduced overall olivocerebellar conduction time, but also disproportionately reduced the conduction time to vermal lobules, which had the longest response latencies prior to myelination. The net result was a nearly uniform conduction time. In contrast, in myelin-deficient rats, conduction time differences to different parts of the cerebellum remained during the same developmental period. Thus myelination is the primary factor in generating a uniform olivocerebellar conduction time. To test the importance of a uniform conduction time for generating synchronous complex spike activity, multiple electrode recordings were obtained from normal and myelin-deficient rats. Average synchrony levels were higher in normal rats than mutants. Thus the uniform conduction time achieved through myelination of olivocerebellar fibers appears to be essential for the normal expression of complex spike synchrony
— id: 39286, year: 2003, vol: 89, page: 2259, stat: Journal Article,

Paranodal interactions regulate expression of sodium channel subtypes and provide a diffusion barrier for the node of Ranvier
Rios, Jose C; Rubin, Marina; St Martin, Mary; Downey, Ryan T; Einheber, Steven; Rosenbluth, Jack; Levinson, S Rock; Bhat, Manzoor; Salzer, James L
2003 Aug 6;23(18):7001-7011, Journal of neuroscience
The node of Ranvier is a distinct domain of myelinated axons that is highly enriched in sodium channels and is critical for impulse propagation. During development, the channel subtypes expressed at the node undergo a transition from Nav1.2 to Nav1.6. Specialized junctions that form between the paranodal glial membranes and axon flank the nodes and are candidates to regulate their maturation and delineate their boundaries. To investigate these roles, we characterized node development in mice deficient in contactin-associated protein (Caspr), an integral junctional component. Paranodes in these mice lack transverse bands, a hallmark of the mature junction, and exhibit progressive disruption of axon-paranodal loop interactions in the CNS. Caspr mutant mice display significant abnormalities at central nodes; components of the nodes progressively disperse along axons, and many nodes fail to mature properly, persistently expressing Nav1.2 rather than Nav1.6. In contrast, PNS nodes are only modestly longer and, although maturation is delayed, eventually all express Nav1.6. Potassium channels are aberrantly clustered in the paranodes; these clusters are lost over time in the CNS, whereas they persist in the PNS. These findings indicate that interactions of the paranodal loops with the axon promote the transition in sodium channel subtypes at CNS nodes and provide a lateral diffusion barrier that, even in the absence of transverse bands, maintains a high concentration of components at the node and the integrity of voltage-gated channel domains
— id: 39114, year: 2003, vol: 23, page: 7001, stat: Journal Article,

Nodal sodium channel domain integrity depends on the conformation of the paranodal junction, not on the presence of transverse bands
Rosenbluth, Jack; Dupree, Jeffrey L; Popko, Brian
2003 Feb;41(3):318-325, Glia
Our understanding of the role that axoglial interactions play in node of Ranvier formation and maintenance remains incomplete. Previous studies of CNS myelinated fibers of CGT-null mice showed abnormalities in the arrangement of paranodal myelin loops and absence of a conspicuous component of the paranodal junction, the ridge-like intercellular transverse bands. Axolemmal sodium channel domains were largely preserved at nodes of Ranvier but displayed some abnormalities in form. Using a combination of freeze-fracture and immunocytochemical methods, we have found additional evidence documenting abnormalities in the size, shape, and location of axolemmal sodium channel clusters in CGT-null mice as well as evidence that these nodal abnormalities are complementary to the organization of paranodal myelin loops, despite the absence of transverse bands. We conclude that the differentiated form of the nodal axolemma and the distribution of axolemmal sodium channels depend on the conformation of paranodal axoglial contacts but not on the presence of transverse bands at the sites of contact
— id: 39328, year: 2003, vol: 41, page: 318, stat: Journal Article,

Dysmyelination induced in vitro by IgM antisulfatide and antigalactocerebroside monoclonal antibodies
Rosenbluth, Jack; Moon, David
2003 Jan 1;71(1):104-109, Journal of neuroscience research
Antiglycolipid antibodies cause a distinctive form of dysmyelination in vivo characterized by marked widening of the myelin period. Such 'expanded' or 'wide-spaced' myelin occurs in peripheral nerves in certain paraproteinemias and in the CNS in multiple sclerosis. We have used an in vitro system to reproduce this pathology under controlled conditions to assess the role of antibody specificity and class and the need for cofactors in generating this kind of lesion in peripheral myelin. Schwann cell myelin formed in vitro around dorsal root ganglion cell axons was exposed for 3-14 days to hybridoma cells that produce specific monoclonal antibodies. Typical wide-spaced myelin developed after exposure to either O4, which produces an IgM antisulfatide antibody, or O1, which produces an IgM antigalactocerebroside antibody. In both cases, the effect was apparent by three days in paranodal as well as internodal myelin, especially in the outer lamellae. This change did not depend on the presence of complement or macrophages in the cultures. Exposure to anti-GalC hybridoma cells, which produce an IgG3 antiglycolipid antibody, did not produce wide-spaced myelin, nor did exposure to hybridoma cells that secrete IgM antibodies directed against a non-myelin antigen. The location and rapidity of the pathologic changes seen after O4 or O1 are consistent with penetration of the antibodies through the external mesaxon of already formed myelin and then between compact lamellae, progressively spreading them apart in the centripetal direction. This in vitro model shows that either of two specific monoclonal IgM antiglycolipid antibodies can alone reproduce a well known form of myelin pathology under defined conditions
— id: 94516, year: 2003, vol: 71, page: 104, stat: Journal Article,

Antibody-mediated CNS demyelination II. Focal spinal cord lesions induced by implantation of an IgM antisulfatide-secreting hybridoma
Rosenbluth, Jack; Schiff, Rolf; Liang, Wei-Lan; Dou, Wenkai
2003 Apr;32(3):265-276, Journal of neurocytology
We showed previously that spinal cord implants of hybridoma cells (O1) that secrete an IgM antigalactocerebroside cause focal multiple-sclerosis-like plaques of demyelination followed by remyelination to form 'shadow plaques' (Rosenbluth et al., 1999). The antibody in that case was directed against a glycolipid present in mature oligodendrocytes and myelin but not in precursor cells. We now report the effects of implanting a different hybridoma (O4) that secretes IgM antibodies directed against sulfatide, a constituent not only of mature myelin and oligodendrocytes but also of late precursor cells, in order to determine whether this hybridoma too would generate focal demyelination and would, in addition, block remyelination. Our results show that focal plaques of demyelination indeed appear after O4 implantation, and that remyelination does occur, but only in cases where the hybridoma cells have degenerated, probably through host rejection. The occurrence of remyelination suggests that oligodendrocyte precursor cells are capable of migrating in rapidly from adjacent areas or that early precursors, not yet expressing sulfatide, remain undamaged within the lesions. In cases where intact hybridoma cells persist at lesion sites, remyelination does not occur. Failure of remyelination in this model thus appears to result from the continuing presence of antimyelin antibodies rather than from depletion of oligodendrocyte precursors
— id: 46247, year: 2003, vol: 32, page: 265, stat: Journal Article,

Receptor protein tyrosine phosphatase (RPTP)-beta is involved in functional recovery from demyelinating lesions of the spinal cord
Harroch, S; Casaccia-Bonnefil, P; Furtado, G; Rosenbluth, J; Chao, M; Lafaille, J; Buxbaum, J; Schlessinger, J
2002 May;(Suppl 1):S84-S84 #P328, Glia
— id: 28182, year: 2002, vol: , page: S84, stat: Journal Article,

A critical role for the protein tyrosine phosphatase receptor type Z in functional recovery from demyelinating lesions
Harroch, Sheila; Furtado, Glaucia C; Brueck, Wolfgang; Rosenbluth, Jack; Lafaille, Juan; Chao, Moses; Buxbaum, Joseph D; Schlessinger, Joseph
2002 Nov;32(3):411-414, Nature genetics
Several lines of evidence suggest that tyrosine phosphorylation is a key element in myelin formation, differentiation of oligodendrocytes and Schwann cells, and recovery from demyelinating lesions. Multiple sclerosis is a demyelinating disease of the human central nervous system, and studies of experimental demyelination indicate that remyelination in vivo requires the local generation, migration or maturation of new oligodendrocytes, or some combination of these. Failure of remyelination in multiple sclerosis could result from the failure of any of these processes or from the death of oligodendrocytes. Ptprz encodes protein tyrosine phosphatase receptor type Z (Ptpz, also designated Rptpbeta), which is expressed primarily in the nervous system but also in oligodendrocytes, astrocytes and neurons. Here we examine the susceptibility of mice deficient in Ptprz to experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. We observe that mice deficient in Ptprz show impaired recovery from EAE induced by myelin oligodendrocyte glycoprotein (MOG) peptide. This sustained paralysis is associated with increased apoptosis of mature oligodendrocytes in the spinal cords of mutant mice at the peak of inflammation. We further demonstrate that expression of PTPRZ1, the human homolog of Ptprz, is induced in multiple sclerosis lesions and that the gene is specifically expressed in remyelinating oligodendrocytes in these lesions. These results support a role for Ptprz in oligodendrocyte survival and in recovery from demyelinating disease
— id: 66616, year: 2002, vol: 32, page: 411, stat: Journal Article,

Sanford Louis Palay: in memoriam
Peters, Alan; Rosenbluth, Jack; Pappas, George; Kruger, Lawrence; Mugnaini, Enrico
2002 Sep-Nov;31(8-9):575-580, Journal of neurocytology
— id: 94515, year: 2002, vol: 31, page: 575, stat: Journal Article,

Distribution and morphology of transgenic mouse oligodendroglial-lineage cells following transplantation into normal and myelin-deficient rat CNS
Schiff, Rolf; Rosenbluth, Jack; Dou, Wen-Kai; Liang, Wei-Lan; Moon, David
2002 Apr 22;446(1):46-57, Journal of comparative neurology
Glial cells from neonatal MbetaP5 transgenic mice, which express bacterial beta-galactosidase (lacZ) under control of the myelin basic protein (MBP) promoter (Gow et al, 1992), were transplanted into the spinal cord or cerebral hemisphere of immunosuppressed normal and myelin-deficient (md) rats in order to assess the ability of the donor cells to survive, migrate, and differentiate within normal compared with myelin-deficient central nervous system (CNS). LacZ+ cells were detected as early as 6-7 days after transplantation into the low thoracic cord and by 10 days had spread rostrally to the brainstem and caudally to the sacral spinal cord. Initially, compact lacZ+ cells, lacking processes, were found associated with small blood vessels and with the glia limitans. Cells of this type persisted throughout the experiment. Later, lacZ+ cells with processes were seen along fiber tracts in the dorsal columns and, after intracerebral injection, subjacent to ventricular ependyma, as well as scattered in cerebral white and gray parenchyma. The extent of spread was comparable in md and normal rats, but in the md group, the success rate was higher, and more cells differentiated into process-bearing oligodendrocytes. Acceptance of xenografts in immunosuppressed recipients equaled that of allografts. The overall spread of grafted cells exceeded that of injected charcoal, indicating active migration. In contrast to earlier studies that identified oligodendrocytes based on morphology alone, this study has allowed us to identify and track oligodendrocytes based on myelin gene expression. We show some oligodendrocytes whose morphology is consistent with classical morphological descriptions, some that resemble astrocytes, and a class of compact perivascular oligodendrocyte-lineage cells that we suggest are migratory
— id: 39690, year: 2002, vol: 446, page: 46, stat: Journal Article,

Axon-glia interactions and the domain organization of myelinated axons requires neurexin IV/Caspr/Paranodin
Bhat MA; Rios JC; Lu Y; Garcia-Fresco GP; Ching W; St Martin M; Li J; Einheber S; Chesler M; Rosenbluth J; Salzer JL; Bellen HJ
2001 May;30(2):369-383, Neuron
Myelinated fibers are organized into distinct domains that are necessary for saltatory conduction. These domains include the nodes of Ranvier and the flanking paranodal regions where glial cells closely appose and form specialized septate-like junctions with axons. These junctions contain a Drosophila Neurexin IV-related protein, Caspr/Paranodin (NCP1). Mice that lack NCP1 exhibit tremor, ataxia, and significant motor paresis. In the absence of NCP1, normal paranodal junctions fail to form, and the organization of the paranodal loops is disrupted. Contactin is undetectable in the paranodes, and K(+) channels are displaced from the juxtaparanodal into the paranodal domains. Loss of NCP1 also results in a severe decrease in peripheral nerve conduction velocity. These results show a critical role for NCP1 in the delineation of specific axonal domains and the axon-glia interactions required for normal saltatory conduction
— id: 27407, year: 2001, vol: 30, page: 369, stat: Journal Article,

No Obvious Abnormality in Mice Deficient in Receptor Protein Tyrosine Phosphatase beta
Harroch S; Palmeri M; Rosenbluth J; Custer A; Okigaki M; Shrager P; Blum M; Buxbaum JD; Schlessinger J
2000 Oct 15;20(20):7706-7715, Molecular & cellular biology
The development of neurons and glia is governed by a multitude of extracellular signals that control protein tyrosine phosphorylation, a process regulated by the action of protein tyrosine kinases and protein tyrosine phosphatases (PTPs). Receptor PTPbeta (RPTPbeta; also known as PTPzeta) is expressed predominantly in the nervous system and exhibits structural features common to cell adhesion proteins, suggesting that this phosphatase participates in cell-cell communication. It has been proposed that the three isoforms of RPTPbeta play a role in regulation of neuronal migration, neurite outgrowth, and gliogenesis. To investigate the biological functions of this PTP, we have generated mice deficient in RPTPbeta. RPTPbeta-deficient mice are viable, are fertile, and showed no gross anatomical alterations in the nervous system or other organs. In contrast to results of in vitro experiments, our study demonstrates that RPTPbeta is not essential for neurite outgrowth and node formation in mice. The ultrastructure of nerves of the central nervous system in RPTPbeta-deficient mice suggests a fragility of myelin. However, conduction velocity was not altered in RPTPbeta-deficient mice. The normal development of neurons and glia in RPTPbeta-deficient mice demonstrates that RPTPbeta function is not necessary for these processes in vivo or that loss of RPTPbeta can be compensated for by other PTPs expressed in the nervous system
— id: 11490, year: 2000, vol: 20, page: 7706, stat: Journal Article,

Biological role of nervous system specific receptor tyrosine phosphatase revealed by analysis of RPTPbeta knockout mice
Harroch, S; Casaccia-Bonnefil, P; Lafaille, J; Chao, M; Custer, A; Shrager, P; Rosenbluth, J; Schlessinger, J
2000 Nov 04-09;26(1-2):?-? Abstract #4018, Abstracts (Society for Neuroscience)
Cell survival, differentiation and migration relies heavily on protein tyrosine phosphorylation of intracellular proteins and is regulated by the activity of kinases and phosphatases. RPTPbeta is a receptor-like protein tyrosine phosphatases composed of an extracellular domain, a single transmembrane domain and a cytoplasmic portion that contains two tyrosine phosphatase domains. Three different isoforms of RPTPbeta are expressed as a result of alternative splicing: a short and a long form that differ by the presence of the spacer region of the extracellular domain and a secreted form lacking phosphatase activity, also known as 3F8 proteoglycan or phosphacan. The pattern of RPTPbeta expression in the developing nervous system, is highly suggestive of its potential role in glial cell differentiation and survival. RPTPbeta is expressed in oligodendrocytes, Schwann cells and astrocytes. Both full-length RPTPbeta phosphatase and phosphacan isoforms are predominantly expressed as chondroitin sulfate proteoglycans in the subventricular zone and in glial cells from E8 throughout development and in the adult nervous system. RPTPbeta forms a ternary complex with contactin and Caspr, localized to the paranodal junctions. It has been suggested that the interaction between RPTPbeta and contactin may mediate bi-directional cellular signals between neurons and glial cells implicating a potential role of RPTPbeta in paranode formation. To investigate RPTPbeta functions, we have generated animals lacking RPTPbeta and demonstrate that these animals lack the three forms of RPTPbeta. Our results provide indications of a role of RPTPbeta in oligodendrocyte survival/differentiation and also an increased axonal sensitivity in disease states. We will discuss the role of RPTPbeta in oligodendrocyte differentiation and axonal growth and its implication for repair after injury
— id: 16057, year: 2000, vol: 26, page: ?, stat: Journal Article,

Biological role of nervous system specific receptor tyrosine phosphatase revealed by analysis of R
Harroch, S; Casaccia-Bonnefil, P; Lafaille, J; Chao, M; Rosenbluth, J; Verdugo-Garcia, JM; Schlessinger, J
2000 DEC ;11(2):401A-401A, Molecular biology of the cell
— id: 55212, year: 2000, vol: 11, page: 401A, stat: Journal Article,

A brief history of myelinated nerve fibers: one hundred and fifty years of controversy
Rosenbluth J
1999 Apr-May;28(4-5):251-262, Journal of neurocytology
The early controversies over myelinated nerve fibers focused on whether nerves are hollow or not, whether the fatty 'marrow' (myelin) is inside the nerve fiber or around it, whether myelin is secreted by the axon or formed by another cell, whether nerve fibers are discrete or part of a syncytial network, whether nodes of Ranvier are present in central myelin or only in peripheral myelin. Since Geren's seminal discovery that peripheral myelin is formed by the Schwann cell plasma membrane wrapped around the axon, the focus has shifted. Myelin is clearly a living cell appendage, and the myelin sheath is dependent upon intercellular interactions not only during its formation, but throughout its lifetime and during pathological processes affecting either the axon or the myelin-forming cell. The myelinated fiber is a functional unit, an exquisite symbiosis, whose ability to perform optimally, in some cases whose very survival, depends on the effects the respective cells exert on one another. How are these interactions mediated? Which structures and functions depend on such interaction and which are independent of it? How do cells of the size and shape of myelin-forming cells cope with their metabolic demands and support their most distal components? What are the mechanisms and mutual consequences of demyelination or axonopathy? Relevant studies have burgeoned with the development of molecular biological and genetic engineering methods, and with improvements in microscopy, in vitro culture and specific immunostaining methods. This introductory essay provides an overview of the structural background and continuing controversies relevant to the articles that follow, which represent a sampling of current work and present new information on the molecular structure, function and pathology of myelin and axoglial interactions
— id: 8648, year: 1999, vol: 28, page: 251, stat: Journal Article,

Antibody-mediated CNS demyelination: focal spinal cord lesions induced by implantation of an IgM anti-galactocerebroside-secreting hybridoma
Rosenbluth J; Schiff R; Liang WL; Dou WK; Moon D
1999 Apr-May;28(4-5):397-416, Journal of neurocytology
O1 hybridoma cells, which secrete an IgM antigalactocerebroside, were implanted into the spinal cord of cyclosporine-treated juvenile or adult rats, and the animals were sacrificed approximately 2-3 wk later. About half the recipient animals developed myelin lesions. In some, sharply circumscribed foci of demyelination formed within the dorsal columns. Cellular reaction consisted of macrophages containing refractile globules in the parenchyma and within enlarged perivascular spaces as well as thickened endothelial cells. 'Shadow plaques' also developed, i.e. regions in which axons were surrounded by thin myelin sheaths, compatible with remyelination. In addition, we found damaged axons, some of which were swollen with organelles, comparable to the enlarged axon profiles seen at sites of constriction or interruption. Compromise of the blood-brain barrier at sites of hybridoma growth was demonstrated by extravasation of Evans blue dye. Discontinuation of cyclosporine was followed by an anti-hybridoma, complement-fixing antibody response within 2-3 d. This model of focal CNS demyelination and remyelination, with evidence of some axon damage, is mediated by a defined IgM antiglycolipid monoclonal antibody secreted within the spinal cord parenchyma. The lesions, which are similar to those of multiple sclerosis, probably result from the interaction between the intrathecally secreted IgM antibody and complement entering from the circulation at foci of compromised blood-brain barrier plus activation of endogenous or hematogenous macrophages via their complement receptors
— id: 8647, year: 1999, vol: 28, page: 397, stat: Journal Article,

Spinal cord dysmyelination induced in vivo by IgM antibodies to three different myelin glycolipids
Rosenbluth J; Liang WL; Schiff R; Dou WK
1997 Jan;19(1):58-66, Glia
It was shown previously (Rosenbluth et al.: J. Neurosci. 16:2635-2641, 1996) that implantation of hybridoma cells that produce an IgM antigalactocerebroside into the spinal cord of young rats results in the development of myelin sheaths with a repeat period approximately 2-3x normal, similar to the abnormal peripheral myelin sheaths seen in human IgM gammopathies. We now present evidence that this effect can be reproduced in the spinal cord by implanting either of two other hybridomas, O4 and A2B5, that secrete, respectively, antisulfatide and antiganglioside IgM antibodies. The formation of expanded CNS myelin thus does not depend on antibodies to galactocerebroside specifically but can be mediated by IgM antibodies that react with other myelin glycolipids as well
— id: 8649, year: 1997, vol: 19, page: 58, stat: Journal Article,

Xenotransplantation of transgenic oligodendrocyte-lineage cells into spinal cord-injured adult rats
Rosenbluth J; Schiff R; Liang WL; Menna G; Young W
1997 Sep;147(1):172-182, Experimental neurology
Spinal cord trauma is associated not only with loss of nerve cells and fibers but also with damage to oligodendrocytes and demyelination. In order to assess the potential of transplanted oligodendrocyte-lineage cells to repair the demyelination that follows spinal cord injury, we have used donor glia derived from a transgenic mouse line containing the LacZ transgene under control of the myelin basic protein promoter. Glia derived from fetal or neonatal transgenic mice were injected into the spinal cords of immunosuppressed adult rats at the site of an experimental traumatic lesion 1-16 days after injury. Cells expressing LacZ were identified 15-18 days later in cryosections rostral and caudal to the transplant site, most conspicuously within white matter defects. Some of these cells within the dorsal columns gave rise to approximately 30- to 60-microns processes, consistent with myelin segments, which are oriented parallel to the fiber tract. Glial transplantation may thus be a feasible means of replacing damaged host oligodendrocytes with donor oligodendrocyte-lineage cells capable of reforming myelin and potentially restoring functional lost as a result of demyelination associated with spinal cord injury
— id: 8276, year: 1997, vol: 147, page: 172, stat: Journal Article,

Expanded CNS myelin sheaths formed in situ in the presence of an IgM antigalactocerebroside-producing hybridoma
Rosenbluth J; Liang WL; Liu Z; Guo D; Schiff R
1996 Apr 15;16(8):2635-2641, Journal of neuroscience
When O1 hybridoma cells, which produce an IgM antigalacto-cerebroside, are implanted into the dorsal columns of 4-8 d rat spinal cord, some of the myelin that subsequently develops in the immediate vicinity displays an abnormal periodicity. The spacings that are seen cluster at approximately 19 nm and 31 nm, roughly two and three times the normal 11 nm spacing. In the expanded sheaths, major dense lines are separated by broad extracellular spaces containing a dense material in which single or double rows of approximately 10 nm circular profiles can be identified, consistent with the 'central rings' of IgM molecules. Because IgM is multivalent, it may serve to link adjacent lamellae together in place of intrinsic myelin molecules that normally interact at close range. Extensive direct contact between myelin components of successive myelin lamellae is thus not essential to signal the growth of the oligodendrocyte membrane or the spiral wrapping of that membrane around axons during myelinogenesis, or to stabilize the myelin spiral that forms
— id: 8650, year: 1996, vol: 16, page: 2635, stat: Journal Article,

Myelin structure in proteolipid protein (PLP)-null mouse spinal cord
Rosenbluth J; Stoffel W; Schiff R
1996 Jul 22;371(2):336-344, Journal of comparative neurology
Fixed preparations of proteolipid protein (PLP)-null mouse spinal cord show myelin sheaths which in some regions consist of typical alternating major dense lines (MDLs) and intermediate lines (ILs) with a repeat period of 10.3 nm. More commonly, the lamellar structure consists of what appears to be a single population of dense lines, having a repeat period of 5.2 nm. These apparently equivalent lines are, however, sometimes distinguishable as MDLs or ILs based on continuity with cytoplasmic or extracellular regions. Focal separations of lamellae at the intermediate line are common. MDLs too may be replaced focally by cytoplasmic pockets, sometimes in the same quadrant over several lamellae, resembling Schmidt-Lanterman clefts. Occasional densities reminiscent of the 'radial component' can be seen. Otherwise, this structure, which is prominent in wild-type myelin, is conspicuously absent. Redundant folding of some lamellae but not others may occur in the same sheath. These observations conform to those made previously on the isolated myelin segments that occur in the myelin-deficient rat central nervous system (CNS), which also lacks PLP. Thus, a compact lamellar structure can be seen in fixed PLP-null myelin, but defects in the apposition of both the extracellular and the cytoplasmic surfaces of the myelin membranes are common. The abnormalities seen suggest a lack of firm intermembrane bonding, resulting in structural instability. PLP-null myelin may therefore be more susceptible than normal myelin to disruption by mechanical or osmotic stresses. Although PLP is not essential for the formation of either major dense lines or intermediate lines, it may play a role in stabilizing the compact structure
— id: 56889, year: 1996, vol: 371, page: 336, stat: Journal Article,

Paranodal structural abnormalities in rat CNS myelin developing in vivo in the presence of implanted O1 hybridoma cells
Rosenbluth J; Liang WL; Liu Z; Guo D; Schiff R
1995 Nov;24(11):818-824, Journal of neurocytology
O1 hybridoma cells, which produce a monoclonal IgM antigalactocerebroside, were implanted into the spinal cords of immature and mature rats and the cords examined 5-24 days later. Study of the younger group, in which myelin was developing at the time of implantation, revealed examples of abnormal myelin sheaths in which the repeat period was markedly increased. The paranodal regions of these abnormal sheaths were superficially normal in configuration; i.e. myelin lamellae terminated one by one as 'terminal loops' that indented the axolemma and formed normal axoglial junctions displaying periodic 'transverse bands'. Neighbouring terminal loops are normally joined by tight junctions that block passage of tracers from the paranodal periaxonal space into the compact myelin, as seen after implantation of a control hybridoma. In the abnormal sheaths that developed after O1 implantation, in contrast, terminal loops were usually widely separated from each other. As a result, multiple pathways from the paranodal periaxonal space into the myelin sheath remained patent, forming potential routes for shunting nodal action currents. This subtle abnormality could thus compromise conduction, even though the sheaths might appear to be normally myelinated at the histological level. Equivalent abnormalities in human neurological diseases, including multiple sclerosis and paraproteinemic neuropathies, could underlie functional loss in the absence of frank demyelination
— id: 6955, year: 1995, vol: 24, page: 818, stat: Journal Article,

Distribution of myelin lipid antigens in adult and developing rat spinal cord
Schiff R; Rosenbluth J
1995 Jul 24;686(2):143-149, Brain research
We examined the distribution of myelin antigens recognized by monoclonal antibodies (mAbs) 01 and 04 in the developing ventral white matter of the cervical spinal cord of the rat using immunogold-labeled ultrathin cryosections. From the beginning of myelination after birth to multilamellar myelin in adult animals, we observed colocalization of 04 and 01 label in myelin. In the oligodendrocyte soma, immunolabel was found primarily over Golgi cisternae. In the oligodendrocyte processes, immunolabeling was also found in the cytoplasm and along the plasmalemma. More cytoplasmic 04 and 01 label was found in the external loop of myelin than in the internal loop. The amount of 01 and 04 label increased over compact myelin in proportion to the number of lamellae, but the label density per unit length of membrane remained approximately the same in compact myelin as in oligodendrocyte plasmalemma. We did not see a concentration gradient for either 04 or 01 label across, or along multilamellar myelin sheaths
— id: 56845, year: 1995, vol: 686, page: 143, stat: Journal Article,

GLYCOLIPID ANTIGENS IN ADULT AND DEVELOPING RAT CNS FIBER TRACTS, DEMONSTRATED BY COLLOIDAL GOLD IMMUNOCYTOCHEMISTRY ON FROZEN THIN-SECTIONS
SCHIFF, R; ROSENBLUTH, J
1995 MAR 9 ;9(3):A251-A251, FASEB journal
— id: 87400, year: 1995, vol: 9, page: A251, stat: Journal Article,

Effects of cerebellar lesions on tonic seizures, tremor and lifespan in myelin-deficient rats
Rosenbluth J; Guo D; Liu Z; Liang WL; Schiff R
1994 Jul 4;650(1):85-92, Brain research
In common with other dysmyelinating mutants, the myelin-deficient rat displays an action tremor and tonic seizures culminating in the death of the animals at approximately 23-26 days. We find that deep lesions of the cerebellar vermis alleviate the manifestations of the myelin deficiency significantly. Such lesions introduced at 20 days or later eliminate both tremor and seizures for periods up to 10 days. Lifespan is prolonged to nearly 30 days, on average, and to 35 days in some cases. Shallow lesions of the vermis or lateral lobe lesions have relatively little effect. Based on these observations we suggest that the cerebellum contributes not only to the action tremor but also to the tonic seizures characteristic of central myelin deficiency. Spontaneous activity originating in myelin-deficient fiber tracts may be carried to the cerebellum and processed there to produce a highly amplified and/or synchronized output to broad areas of the neuraxis. Deep lesions of the vermis presumably interfere with cerebellar output and compromise the cerebellar contribution to the seizures. Tonic seizures and other 'paroxysmal attacks' also occur commonly in human demyelinating diseases including multiple sclerosis [11]. Manipulation of cerebellar output offers a potential approach to the control of such spontaneous activity
— id: 8651, year: 1994, vol: 650, page: 85, stat: Journal Article,

Inhibition of CNS myelin development in vivo by implantation of anti-GalC hybridoma cells
Rosenbluth J; Liu Z; Guo D; Schiff R
1994 Nov;23(11):699-707, Journal of neurocytology
Implantation of hybridoma cells that secrete a monoclonal antigalactocerebroside into the dorsal columns of < or = 9-day-old rat spinal cord results in failure of development of dorsal column myelin in the vicinity of the implant. Clusters of apparently undamaged amyelinated axons remain among the hybridoma cells. Ventral myelin is unaffected. These in vivo results support antibody-mediated inhibition of myelin formation as a potential mechanism underlying failure of remyelination in multiple sclerosis
— id: 6731, year: 1994, vol: 23, page: 699, stat: Journal Article,

Myelin formation by mouse glia in myelin-deficient rats treated with cyclosporine
Rosenbluth J; Liu Z; Guo D; Schiff R
1993 Nov;22(11):967-977, Journal of neurocytology
Previous attempts to generate myelin in the myelin-deficient rat spinal cord by transplanting mouse glia were not successful. In order to determine whether this result was due to graft rejection or to interspecies mismatch of cellular or molecular components at the axoglial junction, we have repeated the experiment in cyclosporine-treated rats. Our results show that in the immunosuppressed hosts, foetal glial xenografts form an abundance of myelin within the dorsal columns at or near the injection site about two weeks after the operation. In some cases, myelination extends virtually across the entire width of the dorsal columns. Ultrastructurally, the myelin sheaths are normal in all respects, including the presence of the 'radial component'. The lateral edges of the myelin lamellae form typical paranodal axoglial junctions, some displaying periodic 'transverse bands'. We infer that previous mouse to rat xenograft failures reflect host immune response rather than mismatch of heterologous junctional components. We also compared foetal, early post-natal and adult xenografts. Foetal donor cells, containing an abundance of precursors but virtually no mature oligodendrocytes, are more effective than neonatal donor cells in forming myelin, and after adult grafts, we found no myelin formation. Thus, in xenografts, as in allografts, foetal precursor cells are far more suitable than glia from mature donors in generating significant amounts of myelin
— id: 8652, year: 1993, vol: 22, page: 967, stat: Journal Article,

Transplantation of labeled fetal spinal cord fragments into juvenile myelin-deficient rat spinal cord
Hasegawa M; Rosenbluth J
1991 Jan;229(1):138-143, Anatomical record
Minced and triturated fragments from the spinal cord of normal rat fetuses (15-18 days gestation) labeled with the fluorescent dye fast blue (FB) were successfully transplanted into juvenile myelin-deficient rat spinal cord under direct observation. Clusters of myelinated fibers were found subsequently in the recipient spinal cord, and, by fluorescence microscopy, clusters of FB-labeled cells were found at corresponding sites. The results indicate that the surgical approach used is suitable for transplantation of tissue fragments into a defined region of juvenile rat spinal cord, that FB can be used to locate the transplanted cells subsequently, and that FB does not interfere with maturation of the donor glia or with myelin formation
— id: 8654, year: 1991, vol: 229, page: 138, stat: Journal Article,

Structural abnormalities in freeze-fractured sciatic nerve fibres of diabetic mice
Shirasaki N; Rosenbluth J
1991 Jul;20(7):573-584, Journal of neurocytology
Nodal and paranodal regions of myelinated sciatic nerve fibres from diabetic (db/db) mice were examined in freeze fracture replicas. In some fibres, the axolemma was found to display abnormalities in the paranodal region. These include shallow, undifferentiated junctional indentations, thinning of the indentations with widening of the non-junctional grooves between them, particle clusters within the non-junctional grooves, and patches in which axolemmal E-face particles are distributed randomly rather than in the form of linear strings within grooves. Nodal structure, in contrast, is hardly affected. Nodal E-face and P-face particle densities in db/db axons are not significantly different from those in age-matched controls, although we found a few examples in which the E-face density fell slightly below the normal range. Occasional fibres showing evidence of paranodal or segmental demyelination were also seen. The results support paranodal pathology as a potential basis for reduced nerve conduction velocity in diabetic nerves but provide no evidence for significant changes in nodal structure or in nodal Na channel density in sciatic nerve fibres of the db/db mouse
— id: 8653, year: 1991, vol: 20, page: 573, stat: Journal Article,

Electrophysiologic changes accompanying Wallerian degeneration in frog sciatic nerve
Levenson D; Rosenbluth J
1990 Jul 23;523(2):230-236, Brain research
The time course of the physiological changes accompanying Wallerian degeneration in the frog is markedly prolonged in comparison with that in mammals. Following transection of frog sciatic nerve, stimulation of the distal segment results in muscle contraction of normal amplitude through day 4, after which tension and EMG signals decline rapidly to levels that are undetectable by day 7. The compound action potential in the severed nerve continues for a much longer period of time, however, persisting as long as approximately 6 weeks. The amplitude remains at normal levels for nearly 3 weeks, after which it declines progressively, approaching zero at approximately 6 weeks. Conduction velocity remains normal in both alpha- and beta-fibers for approximately 3 weeks; thereafter, velocity in the alpha-fibers declines to approximately 71% of normal, and beta-fiber conduction is no longer detectable. Contraction could be elicited by direct stimulation of the muscle during the entire 6-week period of the study. The failure of nerve-mediated muscle activity in the face of persistent nerve conduction could be the result of either a defect in the most distal portions of the nerve fibers or a defect in neuromuscular transmission. These results suggest that EMG evaluation may be more sensitive than nerve conduction studies for clinical assessment of axonopathy at early stages
— id: 8656, year: 1990, vol: 523, page: 230, stat: Journal Article,

Axolemmal abnormalities in myelin mutants
Rosenbluth J
1990 ;605:194-214, Annals of the New York Academy of Sciences
Evidence is reviewed that the paranodal axoglial junction plays important roles in the differentiation and function of myelinated axons. In myelin-deficient axons, ion flux across the axolemma is greater than that in myelinated fibers because a larger proportion of the axolemma is active during continuous, as opposed to saltatory, conduction. In addition, older myelin-deficient rats that have developed spontaneous seizures display small foci of node-like E-face particle accumulations in CNS axons as well as more diffuse regions of increased particle density and number. Assuming that the E-face particles represent sodium channels, such regions could underlie high sodium current density during activity, low threshold for excitation, and increased extracellular potassium accumulation. Depending on the degree of spontaneous channel opening, they could also represent sites of spontaneous generation of activity. The appearance of seizures and their gradual increase in frequency and severity could represent an increase in the number of such regions. In addition, diminution in the dimensions of the extracellular space during maturation would result in increased extracellular resistance, which, together with increasing axonal diameter, would tend to increase the likelihood of ephaptic interaction among neighboring axons as well as the likelihood of extracellular potassium rises to levels that could cause spontaneous activity
— id: 8658, year: 1990, vol: 605, page: 194, stat: Journal Article,

Myelin formation following transplantation of normal fetal glia into myelin-deficient rat spinal cord
Rosenbluth J; Hasegawa M; Shirasaki N; Rosen CL; Liu Z
1990 Oct;19(5):718-730, Journal of neurocytology
Structurally normal myelin sheaths develop in the spinal cord of juvenile myelin-deficient rats (mdr) 11 days after transplantation of normal fetal spinal cord fragments or cultured cells that do not yet express galactocerebroside. Cultures result in more extensive myelin formation, and in both cases the myelin that forms is located primarily at or near the site of transplantation. Myelin formation also occurs after transplantation of postnatal donor tissue, but the extent diminishes with donor age, and none was seen after transplantation of adult donor tissue over the two-week period studied. Injection of killed tissue, tissue derived from mouse donors or an extract of myelin also did not lead to myelin formation. The results imply that myelin formed in the host following transplantation was generated by oligodendrocytes newly differentiated from donor precursor cells rather than by donor oligodendrocytes that were already mature at the time of transplantation or by host oligodendrocytes that took up components of the injected material. We conclude that exogenous fetal glial cell precursors are able to survive, differentiate and form myelin in the environment of the juvenile mdr spinal cord
— id: 8655, year: 1990, vol: 19, page: 718, stat: Journal Article,

X-chromosome monosomy in the myelin-deficient rat mutant
Rosenbluth J; Perle MA; Shirasaki N; Hasegawa M; Wolf ME
1990 Mar;226(3):396-402, Anatomical record
We have identified three examples of female Wistar rats exhibiting the tremor and seizures characteristic of the X-linked myelin deficiency (md) mutation, which is ordinarily seen only in males. Cytogenetic study of two of these animals has shown them to have 41 chromosomes instead of the normal 42. The missing chromosome was identified as an X chromosome by G-banding analysis. These animals thus have an XO genotype comparable to that in Turner's syndrome. Anatomically, one of the animals, which was studied in detail, showed no abnormality of the uterus, and the ovaries, although somewhat smaller than normal, were histologically indistinguishable from those in a normal female rat. No evidence of endocardial fibroelastosis was detected, nor was there any anomaly of the aorta. The myelin deficiency in the central nervous system was comparable to that in hemizygous mutant male rats. XO monosomy in the Wistar rat thus has little effect on phenotype and is more comparable to that in mice than to Turner's syndrome in man. The myelin-deficient rat is useful for studies of X-chromosome monosomy since XO females can readily be identified by the neurological syndrome characteristic of the md mutation
— id: 8657, year: 1990, vol: 226, page: 396, stat: Journal Article,

Spinal cord lesions block seizures or delay their onset in myelin-deficient rats: evidence that generalized tonic seizures can be triggered by abnormal spinal cord activity
Rosenbluth J; Hasegawa M
1989 Feb;103(2):154-157, Experimental neurology
The myelin-deficient mutant rat develops generalized tonic seizures and dies during the fourth postnatal week. Surgical constriction of the lower thoracic spinal cord, performed either after the seizures have appeared or before, eliminates the seizures, or delays their onset, and prolongs the life of the animals. These observations support the view that the seizures in these animals can be triggered by abnormal activity originating in the myelin-deficient spinal cord and can be blocked by preventing that activity from ascending to higher levels. Similar seizures and 'paroxysmal' phenomena occur in other myelin-deficient conditions including multiple sclerosis
— id: 8661, year: 1989, vol: 103, page: 154, stat: Journal Article,

Myelin formation in myelin-deficient rat spinal cord following transplantation of normal fetal spinal cord
Rosenbluth J; Hasegawa M; Schiff R
1989 Feb 13;97(1-2):35-40, Neuroscience letters
Previous studies of the myelin-deficient rat spinal cord have suggested that astrocytes may play a role in preventing the formation of myelin in this mutant, or causing its breakdown. Comparison of mutant and normal littermate spinal cords shows a marked hypertrophy of astrocytes in the mutant in both gray matter and fiber tract regions. Nevertheless, when normal fetal spinal cord fragments are transplanted into mutant host spinal cord, clusters of normal-looking myelin sheaths develop with no sign of attack by host astrocytes
— id: 8660, year: 1989, vol: 97, page: 35, stat: Journal Article,

Extracellular potassium activity and axonal conduction in spinal cord of the myelin-deficient mutant rat
Young W; Rosenbluth J; Wojak JC; Sakatani K; Kim H
1989 Oct;106(1):41-51, Experimental neurology
We recorded somatosensory evoked potentials SEPs), extracellular K+ ionic activity ([K+]e), and K+ clearance rates in the spinal cords of 14 myelin-deficient mutant rats and 16 normal male littermates at 16-41 days after birth. Tested under pentobarbital anesthesia (25 mg/kg ip) and hypothermic conditions (32-34 degrees C), myelin-deficient rats had longer cortical SEP latencies (67 +/- 20 ms) compared to those in normal siblings (48 +/- 15 ms; P less than 0.05). Mean baseline [K+]e levels were 2.6 +/- 0.5 mM in myelin-deficient rats and 2.6 +/- 0.8 mM in normal siblings. Clearance times of KCl solutions injected into the spinal cord were biphasic and exponential. The mean initial and secondary exponential half-times were 1.0 +/- 0.5 and 2.7 +/- 1.7 min for myelin-deficient rats and 0.8 +/- 0.4 and 3.8 +/- 3.2 min for normal siblings. Repetitive sciatic nerve stimulation (2-20 Hz, 2- to 6-s trains) produced 1-3 mM transient [K+]e rises in thoracic and lumbar cords of myelin-deficient rats. The [K+]e rises were largest in the dorsal spinal cord at 200-500 microns depth. The normal siblings had smaller or no stimulus-induced [K+]e rises. In myelin-deficient rats, injection of 1 mM 4-aminopyridine (4-AP) solution into the thoracic spinal cord completely suppressed the stimulus-induced [K+]e and markedly increased spinal and cortical SEP amplitudes for several hours. In the normal siblings, the 4-AP injections transiently blocked spinal conduction for 20-30 min but thereafter enhanced cortical SEP amplitudes for 2-3 h. We conclude that sciatic nerve stimulation produces spinal cord [K+]e rises in myelin-deficient rat larger than those in the normal siblings, that the [K+]e transients represent increased K+ release rather than impaired K+ clearance, and that the K+ ions come from 4-AP blockable sources
— id: 8659, year: 1989, vol: 106, page: 41, stat: Journal Article,

INITIAL SEGMENT STRUCTURE IN FROG SYMPATHETIC-GANGLIA
ABE, H; ROSENBLUTH, J
1988 APR ;220(4):A6-A6, Anatomical record
— id: 41778, year: 1988, vol: 220, page: A6, stat: Journal Article,

Nodal and paranodal structural changes in mouse and rat optic nerve during Wallerian degeneration
Hasegawa M; Rosenbluth J; Ishise J
1988 Jun 14;452(1-2):345-357, Brain research
Ultrastructural changes in nodal and paranodal regions of myelinated mouse and rat optic nerve fibers were followed between 4 h and 28 days during the course of Wallerian degeneration. In the mouse, axoplasmic changes, including accumulation of organelles and segregation of microtubules, were detectable 4 h after transection, and progressed to a maximum level on day 4, at which time many axons were markedly swollen. Dense axoplasm was seen as early as 16 h and was a common feature of degenerating axoplasm at later times. Paranodal changes, which first appeared as early as 16 h after injury, included detachment of terminal loops of myelin from the axolemma, disconnection of terminal loops from compact myelin lamellae and broadening of terminal loops, or separation of the loops from each other, resulting in paranodal elongation. In freeze-fracture replicas, the E-face of the axolemma showed the normal particle distribution as late as days 3-5. By day 8, however, the nodal particles were patchy and the overall nodal particle density was reduced to approximately half normal. Some normal-looking fibers were present at all stages examined, but their number had declined to about half the total population on day 5 and to less than 10% on day 11. In the rat, the overall sequence of events and time course were comparable to those in the mouse. Thus, the morphological changes found follow approximately the same sequence as that described previously in frog nerves, but progress more rapidly in the mouse and rat
— id: 8663, year: 1988, vol: 452, page: 345, stat: Journal Article,

Freeze-fracture study of the perineurium around frog dorsal root ganglia
Matsumoto E; Rosenbluth J
1988 Aug;17(4):425-432, Journal of neurocytology
The perineurium around frog dorsal root ganglia consists of layers of flattened cells separated by extracellular connective tissue elements. The number of layers is smaller than that in the perineurium around adjacent peripheral nerves, and some of the layers are discontinuous, but in both cases, cells in the same layer overlap and form tight junctions with each other, sometimes accompanied by desmosomes or gap junctions. In freeze-fracture replicas the tight junctions between perineurial cells around peripheral nerves consist of 13-91 strands (mean: approximately 38). Some of these are parallel to the cell borders and some are oblique, forming elaborate meshworks. The overall width of each junction averages approximately 12 microns. In contrast, the tight junctions between perineurial cells around ganglia are much narrower, averaging approximately 2 microns in width, and they consist of only 1-14 strands (mean: approximately 6) with few anastomoses and many free ends. These structural differences provide a morphological basis for a less complete diffusion barrier around dorsal root ganglia
— id: 8662, year: 1988, vol: 17, page: 425, stat: Journal Article,

Role of glial cells in the differentiation and function of myelinated axons
Rosenbluth J
1988 ;6(1):3-24, International journal of developmental neuroscience
Myelinated axons are highly differentiated in the vicinity of the node of Ranvier, both structurally and with respect to ion channel distribution. Evidence is reviewed showing that axonal differentiation depends upon two distinct types of interaction between glial cells and the axolemma, one at the node itself, with astrocyte processes, and the second, more extensive one, in the paranodal region, with oligodendrocyte processes. In the peripheral nervous system, Schwann cells fulfill both roles. Glial or Schwann cell abnormalities, due to genetic deficiencies, diseases or experimental procedures, result in corresponding abnormalities in the axolemma and can have devastating effects on nerve fiber function. An example, the myelin-deficient mutant rat, is presented, and the defects underlying the profound and ultimately lethal neurological abnormalities seen in this mutant are discussed in relation to abnormalities in its axoglial interactions
— id: 8665, year: 1988, vol: 6, page: 3, stat: Journal Article,

Spinal cord injury or spinal anesthesia eliminates seizures in myelin-deficient rats
Rosenbluth J; Hasegawa M
1988 Jan 11;84(1):68-72, Neuroscience letters
The generalized tonic seizures that occur in myelin-deficient rats can be eliminated temporarily by spinal cord injury or spinal anesthesia. These observations imply that the seizures in this mutant can be triggered by activity in the spinal cord. The results are consistent with an earlier proposal that axons in myelin-deficient CNS fiber tracts can interact to produce abnormal excitation
— id: 8664, year: 1988, vol: 84, page: 68, stat: Journal Article,

Nodal and paranodal structure during Wallerian degeneration in frog spinal nerve
Ishise J; Rosenbluth J
1987 Aug 18;418(1):85-97, Brain research
The nodal and paranodal regions of myelinated peripheral nerve fibers in frogs were examined at sequential times (1-24 days) during Wallerian degeneration. In the region up to 3 mm distal to the transection, paranodal demyelination and axoplasmic degeneration became apparent on day 4 and progressed to involve most of the nodes by day 8. The E-fracture face of the axolemma showed a patchy distribution of nodal particles and some paranodal demyelination on days 4 and 6. On day 8, nodal particles were evenly distributed at low concentration and the adjacent demyelinated paranodal regions showed a corresponding increase in particle density, suggesting redistribution of the nodal particles. The sequence of changes seen in comparable to that in Wallerian degeneration of central nervous system (CNS) fibers but progressed more rapidly in the peripheral nervous system (PNS). In addition a higher proportion of PNS fibers shows pathological changes at corresponding time periods
— id: 8666, year: 1987, vol: 418, page: 85, stat: Journal Article,

Abnormal axoglial junctions in the myelin-deficient rat mutant
Rosenbluth J
1987 Aug;16(4):497-509, Journal of neurocytology
Although the myelin-deficient rat displays a gross deficiency of myelin in the CNS, occasional myelin segments of moderate thickness can be found. The typical lamellar pattern, consisting of alternating major dense and intermediate lines, is present in some regions of such segments, but the pattern is abnormal elsewhere. Redundant folds are common, and astrocyte processes occur frequently between the myelin sheath and axolemma or within the sheath. In the paranodal region, myelin lamellae occasionally form a palisade of 'terminal loops' against the axolemma, but discrete transverse bands occur only rarely and regular arrays of transverse bands over an extended length have not been seen. 'Reversed' paranodal junctions occur more often. Here the outermost layer of myelin, instead of being closest to the node, is furthest from it, and successive layers form terminal loops that approach the node progressively. These loops face away from the axon and do not contact it. At paranodal junctions of this kind only the innermost loop, or a small number of inner loops, adjoins the axolemma and, as a result, the size of the paranodal axoglial junction is markedly restricted. These defects in the paranodal junction may underlie the intrusion of astrocyte processes from either end of a myelin segment into the internodal periaxonal space and between myelin lamellae. Thus, one of the normal functions of the paranodal junction may be to restrict extension of astrocyte processes into and beneath myelin segments. The myelin-deficient rat also exhibits node-like specializations of the axolemma in association with glial cell processes
— id: 8667, year: 1987, vol: 16, page: 497, stat: Journal Article,

Nodal and paranodal structural changes in frog optic nerve during early Wallerian degeneration
Ishise J; Rosenbluth J
1986 Oct;15(5):657-670, Journal of neurocytology
Ultrastructural changes in the nodal and paranodal regions of myelinated nerve fibres of frog optic nerves were studied during early stages of Wallerian degeneration. The earliest changes seen include retraction of paranodal loops of myelin from the axolemma and disconnection of paranodal myelin loops from myelin lamellae. These paranodal changes are asymmetric around the node and may be more advanced on either the proximal or distal side. Axoplasmic changes, including segregation of microtubules from neurofilaments, disorientation of microtubules and accumulation of abnormal organelles at nodes, appear shortly. In some axons the 'undercoating' along the widened nodal surfaces becomes patchy, and blebs appear in the nodal axolemma. In freeze-fracture replicas a mixture of particle clusters and particle-free areas appears in both E- and P-faces of the nodal axolemma. Blebs remain particle free. Initially, E-face particles remain segregated to the node and are present only at much lower concentrations in the demyelinated paranodal axolemma, suggesting that they are not freely mobile at this stage. Nodal E-face particles begin to decrease on day 5 associated with an increase in particles at the adjacent demyelinated paranode, and by day 11 the particle distribution is uniformly low over the entire extent of the nodal and demyelinated paranodal axolemma. If nodal E-face particles represent sodium channels, as has been proposed, the sequence of changes in Wallerian degeneration would be compatible with a gradual redistribution of nodal sodium channels into the demyelinated paranode.
— id: 8669, year: 1986, vol: 15, page: 657, stat: Journal Article,

Structure of the satellite cell sheath around the cell body, axon hillock, and initial segment of frog dorsal root ganglion cells
Matsumoto E; Rosenbluth J
1986 Jun;215(2):182-191, Anatomical record
The structure of the satellite cell sheath of frog dorsal root ganglion cells was studied in thin sections and freeze-fracture replicas. The sheath around the cell body is composed of thin satellite cell lamellae closely applied to the neuronal plasma membrane. At the axon hillock the sheath divides into outer and inner components separated by a broad space containing a distinctive extracellular matrix and occasional flattened satellite cell processes. The sheath around the initial segment is usually multilayered but less compact than that around the cell body, and in some places it exhibits node-like interruptions. Apart from occasional particle groupings characteristic of tight junctions and gap junctions, the satellite cells display homogeneously distributed intramembranous particles in both fracture faces in all regions of the sheath.
— id: 8670, year: 1986, vol: 215, page: 182, stat: Journal Article,

Ultrastructural localization of laminin in rat sensory ganglia
Schiff R; Rosenbluth J
1986 Dec;34(12):1691-1699, Journal of histochemistry & cytochemistry
We adapted immunocytochemical methods for localization of laminin to examine its disposition in neural tissue at the ultrastructural level. In dorsal root ganglia, laminin was found in basal laminae of the satellite and Schwann cells ensheathing neuronal perikarya and nerve fibers, respectively, and around blood vessels. Within the basal lamina, the immunostain was found in the lamina lucida and lamina densa. Occasional immunostained coated pits were identified in satellite and Schwann cells, but virtually no intracellular label was seen even in freeze-thawed/detergent-permeabilized specimens. In the perineurium, only the basal lamina of the inward-facing surface of the inner-most cell layer was usually stained.
— id: 8668, year: 1986, vol: 34, page: 1691, stat: Journal Article,

Plasma membrane structure at the axon hillock, initial segment and cell body of frog dorsal root ganglion cells
Matsumoto E; Rosenbluth J
1985 Oct;14(5):731-747, Journal of neurocytology
Analysis of the plasmalemma of frog dorsal root ganglion cells by freeze-fracture demonstrates regional differences in the distribution of intramembranous particles. Although P-face particles are distributed rather uniformly, the E-face particle concentration at the cell body (approximately 300 micron -2) is much lower than that at the axon hillock (approximately 900 micron -2), proximal initial segment (approximately 1000 micron -2), or intermediate portion of the initial segment (approximately 800 micron -2). The particle concentrations in the latter regions approach that at the node of Ranvier and, moreover, particle size analysis reveals that the E-face particles, like those at the node, include a large number that are 10 nm or more in diameter. Thin sections reveal patches of a dense undercoating on the cytoplasmic surface of the axolemma in some regions of the initial segment but not the axon hillock. It is concluded from these results that the axon hillock and the initial segment of dorsal root ganglion cells have some of the structural characteristics of the node of Ranvier.
— id: 8673, year: 1985, vol: 14, page: 731, stat: Journal Article,

Intramembranous particle patches in myelin-deficient rat axons
Rosenbluth J
1985 Nov 20;62(1):19-24, Neuroscience letters
Focal accumulations of E-face intramembranous particles occur in spinal cord axons of myelin-deficient rat mutants. These resemble nodal particles and, like them, may represent voltage-sensitive sodium channels. It is proposed that axonal activity at these foci could increase extracellular potassium to the point of triggering activity in adjacent axons. Rapid spread of such potassium-induced activity among bare axons could underlie the seizures and other neurological abnormalities that develop in this mutant. A similar mechanism may account for the paroxysmal attacks sometimes seen in multiple sclerosis.
— id: 8672, year: 1985, vol: 62, page: 19, stat: Journal Article,

Dependence of axolemmal differentiation on contact with glial cells in chronically demyelinated lesions of cat spinal cord
Rosenbluth J; Tao-Cheng JH; Blakemore WF
1985 Dec 9;358(1-2):287-302, Brain research
Chronically demyelinated lesions of cat dorsal columns were created by focal injection of the glial toxin ethidium bromide. Freeze-fracture studies show that the center of the lesion, which is devoid of glial cells and processes, contains axons having neither node-like nor paranodal-type membrane specializations. Near the margin of the lesion, however, where axons are in contact with glial cells, the axolemma sometimes displays focal accumulations of E- and P-face particles resembling those at nodes of Ranvier. In cases where the adjacent cell could be identified, it had the characteristics of an astrocyte. Linear indentations of the axolemma displaying a paracrystalline pattern like that of the paranodal axolemma also occur in the marginal region. Here, the adjacent cell had the characteristics of an oligodendrocyte. These specializations may be closely associated with each other or spatially separate. Normal nodal and paranodal specializations were absent throughout the lesion at all time periods examined. These findings support the view that both the formation and the maintenance of nodal and paranodal axon membrane specializations require contact with glial cells.
— id: 8671, year: 1985, vol: 358, page: 287, stat: Journal Article,

Structural specializations in cat of chronically demyelinated spinal cord axons as seen in freeze-fracture replicas
Rosenbluth J; Blakemore WF
1984 Jul 27;48(2):171-177, Neuroscience letters
Axons in chronically demyelinated spinal cord lesions, induced by ethidium bromide injection, display patches of intramembranous particles and indentations resembling nodal and paranodal axolemmal specializations respectively. Both occur in the marginal region of the lesions where the demyelinated axons are intimately associated with astrocytic and oligodendrocytic processes, and probably correspond to the aberrant node-like and paranodal junctional complexes seen in thin sections of this region. Demyelinated axons in the center of the lesion, which are not in contact with glial processes, do not display these membrane specializations.
— id: 8675, year: 1984, vol: 48, page: 171, stat: Journal Article,

Extranodal particle accumulations in the axolemma of myelinated frog optic axons
Tao-Cheng JH; Rosenbluth J
1984 Aug 13;308(2):289-300, Brain research
Optic nerves of adult frogs were freeze-fractured with the proximal to distal orientation and distances from retina monitored throughout the process. E face particle accumulations are commonly found (approximately 90% of all examples) in the juxtaparanodal portion of the internode (JPI) immediately adjacent to the paranodal junction. The concentration of these particles is usually highest (200-700/micron 2) immediately adjacent to the last strip of the paranodal junction and then decreases over approximately 1-4 micron to the background level (approximately 100/micron 2) of the more remote portions of the internode. Accumulations with high particle concentrations generally extend further into the internode than those with low concentrations. JPI particle accumulations occur with equal frequency in proximal and distal JPIs, and no apparent difference was seen between optic nerve segments adjacent to or distant from the retina. The majority of the JPI particles are large (10 nm or more in diameter), and they resemble the large nodal particles in size and shape. Particle size analysis in different areas of the internode shows that the concentration of small particles does not change significantly along the internode (including the JPI), but the concentration of large particles is significantly higher in the immediate JPI (140-600/micron 2) than in internodal regions (30-55/micron 2). Thus, the high particle concentration at the JPI region is mainly due to the accumulation of large particles. Such accumulations also occur frequently in irregularly shaped 'lakes' between paranodal junctional strips. Here too the particles are primarily large, and the accumulations occur equally in segments adjacent to or distant from the retina and in both proximal and distal paranodal regions. Heminodes occur in all segments of the frog optic nerve. Most of these lack typical nodal specializations.
— id: 8674, year: 1984, vol: 308, page: 289, stat: Journal Article,

Electrophysiology and morphology of myelinated nerve fibers. V. Intramembranous particle distribution in nerve fiber membranes
Rosenbluth J
1983 Sep 15;39(9):953-963, Experientia
— id: 8676, year: 1983, vol: 39, page: 953, stat: Journal Article,

Axolemmal differentiation in myelinated fibers of rat peripheral nerves
Tao-Cheng JH; Rosenbluth J
1983 Sep;285(3):251-263, Brain research
In developing rat peripheral fibers, nodal specialization appears early, prior to myelin compaction, and is first detected as a junction between the axon and the overhanging Schwann cell process characterized by a uniformly wide (approximately 18 nm) intercellular gap containing a patchy dense substance and a cytoplasmic undercoating subjacent to the axolemma. The gap width is rather consistent but the axolemmal undercoating is more variable and lower in density than that found at more mature nodes of Ranvier, and it is also highly variable in length, ranging from 0.5 to 3 micron. The outermost Schwann cell layer is usually prominent with a large volume of cytoplasm and many organelles. In freeze-fracture replicas, modal specializations are characterized by accumulations of large (approximately 10 nm) particles in the axolemma, especially the E face, but immature nodes generally have a lower particle concentration than mature nodes. No node-like particle aggregates have been found in axons not intimately associated with Schwann cells. Mature paranodal axon-Schwann cell junctions are usually formed first by the loops closest to the node and are characterized by a 2-3 nm gap between the apposed membranes, periodic intercellular densities (transverse bands) in the gap and cisternae flattened against the junctional Schwann cell membrane. The loops further removed from the node display a wider gap containing irregularly spaced or diffuse intercellular densities, or none. Mature junctions appear relatively late in the rat, and it is not unusual to find developing nodes with several Schwann cell loops present that do not indent the axolemma significantly and are not associated with the paracrystalline pattern characteristic of the mature junctional axolemma. In such instances, the nodal particle aggregates do not have sharply circumscribed boundaries. The majority of the developing nodes are asymmetric with one paranodal segment more mature than the other.
— id: 8677, year: 1983, vol: 285, page: 251, stat: Journal Article,

Anionic sites on the surface of frog ependymal astrocytes and mouse ependymal cells
Korte GE; Rosenbluth J
1982 Sep;204(1):95-100, Anatomical record
The binding of colloidal iron hydroxide (CI) and ruthenium red (RR) to the plasma membrane of frog ependymal astrocytes was examined by electron microscopy. Positively charged CI and RR bind to the external surface of the plasma membrane of all parts of the ependymal astrocyte. Prior treatment with neuraminidase markedly reduces the number of bound CI particles, suggesting that the sialic acid of carbohydrates associated with the cell surface is responsible for much of the CI binding. Comparable observations were made on mouse ependymal cells. These findings indicate that an anionic, carbohydrate-rich cell coat occurs on the plasma membrane of amphibian ependymal astrocytes and mammalian ependymal cells. This cell coat may be related to transport, barrier, or receptive functions of ependymal cells.
— id: 8678, year: 1982, vol: 204, page: 95, stat: Journal Article,

Development of nodal and paranodal membrane specializations in amphibian peripheral nerves
Tao-Cheng JH; Rosenbluth J
1982 Apr;255(4):577-594, Brain research
Peripheral nerves from the hind legs of frog tadpoles were examined in order to ascertain the pattern of development of nodal and paranodal specializations in myelinated fibers. In thin sections the earliest detectable node-related specializations resemble 'intermediate' junctions between axons and Schwann cell processes. These occur in individually ensheathed axons near the edges of the sheath segments and could represent early nodal or paranodal components or transient structures. The characteristic nodal 'undercoating' is indistinct and highly variable in thickness in immature fibers and its density is lower in developing nodes than in adult nodes. Corresponding freeze-fracture replicas of developing axons demonstrate aggregates of nodal E face particles whose concentration is lower than that in the adult. Such aggregates usually occur immediately adjacent to Schwann cell indentations, even though early in development the latter may not exhibit the paracrystalline pattern seen in the adult paranodal axolemma. On rare occasions, node-like particle aggregates and presumptive nodal undercoatings have been observed without recognizable paranodal junctions or indentations nearby. However, neither specialization has been found in axons not individually ensheathed by Schwann cells. Paranodal Schwann cell loops are widely separated and irregularly arranged in the developing nodes, and the paranodal regions flanking a node usually mature asymmetrically. Differentiated paranodal junctions appear early in axons ensheathed by only a few loose Schwann cell lamellae. However, such junctions are not formed by all paranodal loops; they consistently appear first in the loops close to the node and only later in those further removed. No junctional specialization has been observed in either the axolemma or the Schwann cell membrane without the close association of the other.
— id: 8679, year: 1982, vol: 255, page: 577, stat: Journal Article,

Ependymal astrocytes in the frog cerebellum
Korte GE; Rosenbluth J
1981 Feb;199(2):267-279, Anatomical record
We have examined the ependymal astrocytes of the frog cerebellar cortex in thin sections and freeze-fracture replicas. The somata border the fourth ventricle and give rise to basal processes whose daughter branches cross the molecular layer and terminate as subpial endfeet. Irregular lamellar appendages arise from the basal processes and their branches. In the molecular layer the appendages selectively ensheath apposed parallel fiber boutons and Purkinje cell dendritic spines. Other appendages ramify throughout the neuropil, some contributing to extensive pericapillary sheaths. Freeze-fractured ependymal astrocyte plasma membrane consistently has a greater concentration of intramembranous particles (IMPs) and IMPs of larger mean size than neuronal plasma membrane in the same replicas. Like the astrocytes of the mammalian central nervous system, frog ependymal astrocytes form numerous gap junctions with each other. However, orthogonal arrays of IMPs ('assemblies') were not observed. Ependymal cells in the frog cerebellum combine the morphology, and probably the functions, of both ependymal cells and astrocytes.
— id: 8681, year: 1981, vol: 199, page: 267, stat: Journal Article,

Axoglial junctions in the mouse mutant Shiverer
Rosenbluth J
1981 Mar 16;208(2):283-297, Brain research
Analysis of Shiverer central nervous tissue by the freeze-fracture method shows that axoglial junctions of the type found normally in the paranodal region occur commonly despite the gross reduction in myelin. On a substructural level these junctions appear identical to those that form between paranodal oligodendroglial processes and axolemma. On a grosser level, however, they are bizarre in shape, arrangement and distribution. Isolated glial processes, or small sheaves of them, course among axons and form such junctions in an irregular patchy manner, usually without apparent relationship to paranodal regions. These aberrant junctions may be oriented transversely, obliquely or longitudinally with respect to the axonal axis. Axolemmal E face particle accumulations, which characterize normal nodes of Ranvier, are usually not found in the membrane adjacent to the aberrant junctional patches. Thus, axoglial junctional specializations of the paranodal type can form in this mutant in the absence of the myelin proteins that are deficient in Shiverer, and such junctions may appear in areas not related to other paranodal or nodal structures. The relevance of these findings to differentiation of the axolemma and to the neurological defects in this mutation is discussed.
— id: 8680, year: 1981, vol: 208, page: 283, stat: Journal Article,

Freeze-fracture approaches to ionophore localization in normal and myelin-deficient nerves
Rosenbluth J
1981 ;31:391-418, Advances in neurology
(1) The principal result of freeze-fracture studies of myelinated axons is that the axolemma is clearly not uniform in its structure, but rather is highly differentiated in both paranodal and nodal regions. Thus, it is no longer correct to assume that the special physiological properties of myelinated nerve fibers derive only from the presence of the myelin sheath. The inhomogeneity of the axolemma must also be taken into account. (2) The nodal axolemma is characterized by a population of large intramembranous particles primarily in the E fracture face that may correspond to the voltage sensitive sodium channels known to be concentrated there. (3) Significant numbers of such particles also frequently occur in paranodal 'lakes' and in the internodal axolemma immediately adjacent to the paranodal region. These are probably accessible, albeit slowly, by way of the narrow extracellular cleft between the paranodal junctional membranes. (4) In the absence of ensheathment by myelinating cells, axons fail to develop normal nodal and paranodal membrane specializations. (5) When ensheathed by abnormal myelinating cells, corresponding abnormalities develop in both nodal and paranodal specializations of the axolemma. (6) Demyelination results in dedifferentiation of axolemmal specializations. (7) It is concluded that development and maintenance of normal axolemmal differentiation requires interaction of the axon with myelinating cells. These cells thus serve not only to produce myelin but also to regulate axolemmal differentiation. Alterations in axolemmal structure following demyelination may significantly affect the physiological properties of the axons. Specifically, ionophore redistribution may underlie the development of either continuous or nonuniform conduction in some demyelinated fibers.
— id: 8682, year: 1981, vol: 31, page: 391, stat: Journal Article,

PARTICLE DISTRIBUTION AT HEMINODES IN DYSTROPHIC MOUSE NERVES
Rosenbluth, J
1981 ;199(3):A216-A216, Anatomical record
— id: 30275, year: 1981, vol: 199, page: A216, stat: Journal Article,

Freeze-fracture study of the postsynaptic membrane of the cerebellar mossy fiber synapse in the frog
Korte GE; Rosenbluth J
1980 Oct 1;193(3):689-700, Journal of comparative neurology
We have examined the postsynaptic membrane of the synaptic junctions of frog cerebellar mossy fibers by electron microscopy of freeze-fracture replicas and thin sections. The intramembranous particles (imps) in the E fracture face of the postsynaptic membrane are approximately 10 nm in size and form conspicuous aggregates which we classified as macular, annular, or anastomotic in form, according to the occurrence and placement of imp-free 'windows' within the aggregate. The size and shape of the aggregates appear related in that the area of macular aggregates is consistently smaller than the area of annular or anastomotic aggregates. Measurements of aggregate area range from 0.06 to 0.75 micrometer2. The variable size and shape of the imp aggregate in the postsynaptic membrane sets it apart from other excitatory synapses in the central nervous system, where macular aggregates are usually described. Examination of serial thin sections suggests that the shape of the postsynaptic density is equivalent to that of the imp aggregate observed in the postsynaptic membrane by freeze-fracture. This supports the notion that the region of postsynaptic membrane associated with the postsynaptic density in thin sections corresponds to the particle-rich regions of E face membrane observed in freeze-fracture replicas.
— id: 8686, year: 1980, vol: 193, page: 689, stat: Journal Article,

Central myelin in the mouse mutant shiverer
Rosenbluth J
1980 Dec 1;194(3):639-648, Journal of comparative neurology
The spinal cord, optic nerves, and cerebellum of the mouse mutant Shiverer were examined by electron microscopy of thin sections. Although central nervous system myelin is grossly deficient in amount, none of its basic structural elements are missing. Regions of compact myelin can be found composed of several layers of alternating major dense lines and intermediate lines repeating with normal periodicity. The 'radial component' consisting of periodic thickenings of the intermediate line aligned through several lamellae was also identified. Axoglial junctions characteristic of the type found in paranodal regions are present in greater than normal numbers but occur in aberrant locations. Myelin sheaths have marked reduced numbers of lamellae, which often contain cytoplasm, terminate in cytoplasmic 'loops' within and around myelin sheaths, and do not completely encircle axons. In addition, membranous debris appears within neuronal and glial profiles, suggesting some degree of myelin breakdown. Thus, the protein lacks in this mutant appear not to be associated with discrete deficiencies of specific structural components but rather with a variety of quantitative changes and irregularity of form.
— id: 8683, year: 1980, vol: 194, page: 639, stat: Journal Article,

Peripheral myelin in the mouse mutant Shiverer
Rosenbluth J
1980 Oct 1;193(3):729-739, Journal of comparative neurology
The mouse mutant Shiverer has been shown previously to lack myelin basic protein and other myelin proteins in both the peripheral and central nervous systems. Examination by electron microscopy shows that the peripheral nervous system, in contrast to the markedly abnormal central nervous system, is grossly normal. Myelin sheaths are of the usual thickness and exhibit normal periodic structure consisting of alternating major dense and intermediate lines. Subtle abnormalities do occur, however, consisting of increased numbers of cytoplasm-containing lamellae, aberrant terminations of myelin lamellae in internodal regions, invagination of the axon by the inner tongue of the myelin sheath, myelin debris in both axon and Schwann cells, and disruption of outer myelin lamellae. Such changes have been seen previously in various types of neuropathy and are not pathognomonic of the Shiverer mutation. Despite the absence of myelin basic protein, the peripheral manifestations of this gene are relatively minor and probably not severe enough to compromise peripheral nerve function significantly.
— id: 8685, year: 1980, vol: 193, page: 729, stat: Journal Article,

Nodal and paranodal membrane structure in complementary freeze-fracture replicas of amphibian peripheral nerves
Tao-Cheng JH; Rosenbluth J
1980 Oct 20;199(2):249-265, Brain research
Complementary freeze-fracture replicas of frog peripheral nerves have revealed new details of membrane structures at the node of Ranvier and paranodal axon-Schwann cell junction. At the node both E and P fracture faces of the axolemma have high particle concentrations (approximately 1350/sq. micron and 1600/sq. micron respectively) and these particles do not overlap when tracings from the respective fracture faces are superimposed. A high proportion of the E face particles are large (> 9.5 nm) and cast long shadows while the proportion of large particles in the P face is much lower. In the paranodal region the diagonal pattern of parallel rows in the junctional axolemma always has the same orientation within a given fracture face. In the E face, the parallel rows form a positive (+ 30 degrees) angle to the groove below and in the P face, a negative (-30 degrees) angle to the ridge above. This implies that the diagonal pattern derives from asymmetric subunits that are able to associate along only one axis and are unable to 'flip over' with respect to the junctional membranes.
— id: 8684, year: 1980, vol: 199, page: 249, stat: Journal Article,

Aberrant axon-Schwann cell junctions in dystrophic mouse nerves
Rosenbluth J
1979 Oct;8(5):655-672, Journal of neurocytology
'Amyelinated' axons in the spinal roots of dystrophic mouse nerves lack typical nodal and paranodal membrane specializations. However, at the periphery of the amyelinated bundles some of the naked axons form aberrant junctions with Schwann cells belonging to neighbouring myelinated axons. These junctions are characterized by a narrow intercellular cleft containing regularly-spaced densities that closely resemble the 'transverse bands' found at paranodal axoglial junctions with respect to both configuration and spacing. In addition, the Schwann cells sometimes extend fingerlike projections towards amyelinated axons in regions where the axolemma has a dense cytoplasmic undercoating. Such regions resemble nodes of Ranvier, where Schwann cell processes interlace over the axolemma. Freeze-fracture replicas show no typical nodal or paranodal membrane specializations in the amyelinated fibres where they are apposed to each other. However, isolated paracrystalline patches of membrane occur corresponding to the aberrant junctions between amyelinated axons and Schwann cells at the periphery of the bundles. The observations show that structural differentiation of the axolemma occurs only where axons are in intimate contact with myelinating cells and does not develop independently in the amyelinated regions. Sodium channels, which are normally concentrated in the specialized nodal membrane, are, therefore, probably distributed uniformly along the amyelinated axon segments that show no sign of such regional differentiation. In addition, it is shown that Schwann cells are capable of forming specialized junctions with more than one axon at the same time.
— id: 8687, year: 1979, vol: 8, page: 655, stat: Journal Article,

NEW STRUCTURAL DETAILS OF AXON-SCHWANN CELL-JUNCTIONS
Rosenbluth, J
1979 ;193(3):667-668, Anatomical record
— id: 30033, year: 1979, vol: 193, page: 667, stat: Journal Article,

Glial membrane specializations in extraparanodal regions
Rosenbluth J
1978 Dec;7(6):709-719, Journal of neurocytology
Previous freeze-fracture studies of central myelinated nerve fibres have demonstrated a distinctive junction in the paranodal region formed between the terminal loops of the glial cell and the axolemma. This unique junction is characterized by the presence of diagonally oriented rows of particles in the P face and to a lesser extent in the E face of the glial cell and an equivalent pattern in the axolemma. In both, the rows are spaced at 250--300 A intervals. Although this junction was originally thought to be peculiar to the paranodal region, examples of the same pattern have now been seen in extraparanodal regions in the central nervous system where they appear as circumscribed patches of membrane exhibiting a pattern identical to that in the paranodal glial loops. All examples found were in the immediate vicinity of myelinated nerve fibres and in one case the membrane containing the specialized patch was identified as a lamella of a myelin sheath. These observations constitute evidence that this distinctive membrane specialization is not limited to the paranodal axoglial junction but can also be found in glial membrane specialization is not limited to the paranodal axoglial junction but can also be found in glial membranes not in immediate contact with the specialized membrane of the paranodal axolemma.
— id: 8688, year: 1978, vol: 7, page: 709, stat: Journal Article,

Particle arrays in earthworm postjunctional membranes
Rosenbluth J
1978 Jan;76(1):76-86, Journal of cell biology
Analysis of freeze-fractured earthworm body wall muscle reveals distinctive trough-shaped concavities in the protoplasmic leaflet of the muscle cell membrane which contain diagonally oriented rows of particles sometimes in highly ordered arrays. The troughs correspond to the concave postjunctional patches of sarcolemma seen previously in thin sections of myoneural junctions identified as cholinergic, and the intramembranous particles within the troughs correspond in concentration and arrangement to granular elements present in the outer dense lamina of the postjunctional membrane which were interpreted as acetylcholine receptors. The freeze-fracture data provide a more accurate picture of the arrangement of these putative receptors within the plane of the membrane, and indicate also that they extend into the membrane at least as far as its hydrophobic layer.
— id: 8690, year: 1978, vol: 76, page: 76, stat: Journal Article,

Environmental influences on drinking by college students in a college pub: behavioral observation in the natural environment
Rosenbluth J; Nathan PE; Lawson DM
1978 ;3(2):117-121, Addictive behaviors
— id: 8689, year: 1978, vol: 3, page: 117, stat: Journal Article,

SEPTATE JUNCTIONS BETWEEN SCHWANN-CELLS AND AMYELINATED AXONS IN DYSTROPHIC MOUSE NERVES
Rosenbluth, J
1978 ;79(2):A101-A101, Journal of cell biology
— id: 29871, year: 1978, vol: 79, page: A101, stat: Journal Article,

GLIAL MEMBRANE SPECIALIZATIONS IN FREEZE-FRACTURE REPLICAS OF FROG BRAIN
Rosenbluth, J
1977 ;75(2):A240-A240, Journal of cell biology
— id: 29570, year: 1977, vol: 75, page: A240, stat: Journal Article,

Intramembranous particle distribution at the node of Ranvier and adjacent axolemma in myelinated axons of the frog brain
Rosenbluth J
1976 Dec;5(6):731-745, Journal of neurocytology
The plasma membrane of myelinated axons in the frog brain has been examined by the freeze-fracture technique. The cytoplasmic leaflet of the axolemma contains numerous randomly distributed particles in nodal and internodal regions but relatively fewer particles in the axoglial junctional portion of the paranodal region. Particle distribution is even less uniform in the outer leaflet of the axolemma, which contains a low concentration of particles in the internodal region and a relatively high concentration at the node of Ranvier (approximately 1200 particles mum-2). The nodal particles tend to be larger than most intramembranous particles, approaching 200 A diameter. The paranodal region of the leaflet is virtually devoid of such particles except in the narrow helical 'groove' which faces extracellular clefts between terminating glial processes. In places this pathway widens to form 'lakes' up to approximately 0.3 mum2 area which contain large numbers of large particles resembling those at the node. The concentration of particles at the node is in the same range as the concentration of sodium channels estimated to be in this region and it is suggested on the basis of their location and concentration that these particles represent ionophores. The distribution of particles in the paranodal region suggests that the large intramembranous particles do not have free access to the axoglial junctional portion of the membrane and therefore the movement of such particles along the paranodal region of the membrane may occur primarily in the membrane of the 'groove' spiraling through this portion of the axolemma. Such a restriction in surface area for particle movements on either side of the node of Ranvier could result in trapping of particles at the node and thus contribute to their concentration in the nodal axolemma.
— id: 8691, year: 1976, vol: 5, page: 731, stat: Journal Article,

STRUCTURE OF ELECTRICALLY EXCITABLE MEMBRANE AT NODES OF RANVIER IN FROG BRAIN
Rosenbluth, J
1976 ;70(2):A182-A182, Journal of cell biology
— id: 29451, year: 1976, vol: 70, page: A182, stat: Journal Article,

Ontogenetic studies of a catecholamine-containing nucleus of the toad hypothalamus relation to metamorphosis
McKenna OC; Rosenbluth J
1975 Mar;46(3):496-505, Experimental neurology
— id: 8693, year: 1975, vol: 46, page: 496, stat: Journal Article,

Synaptic membrane structure in Torpedo electric organ
Rosenbluth J
1975 Dec;4(6):697-712, Journal of neurocytology
The innervated and noninnervated membranes of Torpedo electrocytes have been examined by electron microscopy of thin-sectioned and freeze-fractured specimens. The ventral innervated membrane is approximately 120 A thick and is characterized by an unusually broad outer dense lamina (approximately 60 A) in which a granular substructure can be resolved. The granules are approximately 70 A in diameter and are spaced irregularly. The same membrane specialization was noted in a previous study of amphibian myoneural junctions, and it was proposed then that the granular elements represent ACh receptor molecules. The morphologically equivalent structures presumably have the same significance in the Torpedo electric organ. However, in this case the specialized membrane covers the entire innervated surface, leading to the conclusion that high concentrations of receptors occur normally in extrajunctional as well as post-junctional regions of the innervated membrane of the electrocyte. In replicas of freeze-fractured specimens, the A face of this membrane is covered with large particles having the same distribution and approximate concentration as the granules visible in thin sections, indicating that the granules visible at the outer surface of the membrane extend at least into the hydrophobic middle layer of the membrane. The cytoplasmic surface of this membrane has an amorphous coating into which 'decorated' cytoplasmic filaments insert. Synaptic vesicle and axon terminal membranes also contain granules visible in thin sections but with a much sparser distribution. These probably correspond to the intramembranous particles seen in freeze-fractured specimens. Vesicles are occasionally attached to the axolemma by thin linear strands.
— id: 8692, year: 1975, vol: 4, page: 697, stat: Journal Article,

Cytological evidence for catecholamine-containing sensory cells bordering the ventricle of the toad hypothalamus
McKenna OC; Rosenbluth J
1974 Mar 15;154(2):133-148, Journal of comparative neurology
— id: 8695, year: 1974, vol: 154, page: 133, stat: Journal Article,

SUBSTRUCTURE OF A VERTEBRATE MOTOR ENDPLATE MEMBRANE
ROSENBLU.J
1974 ;178(2):522-522, Anatomical record
— id: 47019, year: 1974, vol: 178, page: 522, stat: Journal Article,

Substructure of amphibian motor end plate. Evidence for a granular component projecting from the outer surface of the receptive membrane
Rosenbluth J
1974 Sep;62(3):755-766, Journal of cell biology
— id: 8694, year: 1974, vol: 62, page: 755, stat: Journal Article,

Golgi impregnation study of a new catecholamine-containing cell type in the toad hypothalamus
McKenna OC; Pinner-Poole B; Rosenbluth J
1973 Sep;177(1):1-13, Anatomical record
— id: 8698, year: 1973, vol: 177, page: 1, stat: Journal Article,

Myoneural and intermuscular junctions in a molluscan smooth muscle
McKenna OC; Rosenbluth J
1973 Mar;42(5):434-450, Journal of ultrastructure research
— id: 8699, year: 1973, vol: 42, page: 434, stat: Journal Article,

MEMBRANE SPECIALIZATIONS AT MYONEURAL JUNCTIONS
ROSENBLU.J
1973 ;175(2):428-&, Anatomical record
— id: 46804, year: 1973, vol: 175, page: 428, stat: Journal Article,

POSTJUNCTIONAL MEMBRANE SPECIALIZATION AT SYNAPTIC JUNCTIONS IN AMPHIBIAN CENTRAL NERVOUS-SYSTEM
ROSENBLU.J
1973 ;59(2):A291-A291, Journal of cell biology
— id: 46738, year: 1973, vol: 59, page: A291, stat: Journal Article,

Membrane specialization at an insect myoneural junction
Rosenbluth J
1973 Oct;59(1):143-149, Journal of cell biology
— id: 8697, year: 1973, vol: 59, page: 143, stat: Journal Article,

Postjunctional membrane specialization at cholinergic myoneural junctions in the leech
Rosenbluth J
1973 Oct 15;151(4):399-405, Journal of comparative neurology
— id: 8696, year: 1973, vol: 151, page: 399, stat: Journal Article,

Ultrastructure of developing Xenopus retina before and after ganglion cell specification
Grillo MA; Rosenbluth J
1972 Jun;145(2):131-140, Journal of comparative neurology
— id: 8702, year: 1972, vol: 145, page: 131, stat: Journal Article,

UNPHYSIOLOGICAL CONDITIONS FAVORING AGGREGATION OF SMOOTH-MUSCLE MYOSIN IN-SITU
ROSENBLU.J
1972 ;55(2):A220-A220, Journal of cell biology
— id: 46843, year: 1972, vol: 55, page: A220, stat: Journal Article,

Myoneural junctions of two ultrastructurally distinct types in earthworm body wall muscle
Rosenbluth J
1972 Sep;54(3):566-579, Journal of cell biology
— id: 8701, year: 1972, vol: 54, page: 566, stat: Journal Article,

Myoneural junctions in larval ascidian tail
Tannenbaum AS; Rosenbluth J
1972 Oct 15;28(10):1210-1212, Experientia
— id: 8700, year: 1972, vol: 28, page: 1210, stat: Journal Article,

Characterization of an unusual catecholamine-containing cell type in the toad hypothalamus. A correlated ultrastructural and fluorescence histochemical study
McKenna, O C; Rosenbluth, J
1971 Mar;48(3):650-672, Journal of cell biology
— id: 8704, year: 1971, vol: 48, page: 650, stat: Journal Article,

Myosin-like aggregates in trypsin-treated smooth muscle cells
Rosenbluth, J
1971 Jan;48(1):174-188, Journal of cell biology
— id: 8705, year: 1971, vol: 48, page: 174, stat: Journal Article,

Myosin-like tactoids in trypsin-treated blood platelets
Rosenbluth, J
1971 Sep;50(3):900-904, Journal of cell biology
— id: 8703, year: 1971, vol: 50, page: 900, stat: Journal Article,

Stress relaxation in Ascaris obliquely striated muscle
Rosenbluth J; Eberstein A; Friedman J
1970 Jan 15;32(2):295-299, Comparative biochemistry & physiology
— id: 8706, year: 1970, vol: 32, page: 295, stat: Journal Article,

Sarcoplasmic reticulum of an unusually fast-acting crustacean muscle
Rosenbluth J
1969 Aug;42(2):534-547, Journal of cell biology
— id: 8708, year: 1969, vol: 42, page: 534, stat: Journal Article,

Ultrastructure of dyads in muscle fibers of Ascaris lumbricoides
Rosenbluth J
1969 Sep;42(3):817-825, Journal of cell biology
— id: 8707, year: 1969, vol: 42, page: 817, stat: Journal Article,

OBLIQUELY STRIATED MUSCLE : IV. Sarcoplasmic Reticulum, Contractile Apparatus, and Endomysium of the Body Muscle of a Polychaete, Glycera, in Relation to Its Speed
Rosenbluth, J
1968 Jan 1;36(1):245-259, Journal of cell biology
Body muscle cells of the bloodworm Glycera, a polychaete annelid, were studied by electron microscopy and compared with muscle cells of the more slowly acting nematode Ascaris, which have been described previously. Both muscles are obliquely striated. The predominant type of bloodworm fiber is characterized by a prominent transversely oriented sarcoplasmic reticulum with numerous dyads at the surface of each cell. Thick myofilaments are approximately 3 micro long and overlap along approximately 60% of their length in extended fibers and approximately 80% in shortened fibers. There is virtually no endomysium and very little intracellular skeleton, and the cells are attached by desmosomes to one another rather than to connective tissue. Dense bodies are absent from the fibers and in their place are Z lines, which are truly linear rather than planar. Scattered among the predominant fibers are others, less orderly in arrangement, in which the SR is much less prominent and in which the thick filaments are thicker and longer and overlap to an even smaller degree. It is suggested that physiological differences between bloodworm and Ascaris muscles derive from differences in the proportion of series to parallel linkages between the contractile elements, differences in the amount and disposition of the SR, and differences in the impedance to shear within the myofibrils
— id: 110654, year: 1968, vol: 36, page: 245, stat: Journal Article,

Obliquely striated muscle. 3. Contraction mechanism of Ascaris body muscle
Rosenbluth J
1967 Jul;34(1):15-33, Journal of cell biology
— id: 8709, year: 1967, vol: 34, page: 15, stat: Journal Article,

Redundant myelin sheaths and other ultrastructural features of the toad cerebellum
Rosenbluth J
1966 Jan;28(1):73-93, Journal of cell biology
— id: 8710, year: 1966, vol: 28, page: 73, stat: Journal Article,

Ultrastructural organization of obliquely striated muscle fibers in Ascaris lumbricoides
Rosenbluth J
1965 Jun;25(3):495-515, Journal of cell biology
— id: 8712, year: 1965, vol: 25, page: 495, stat: Journal Article,

Ultrastructure of somatic muscle cells in Ascaris lumbricoides. II. Intermuscular junctions, neuromuscular junctions, and glycogen stores
Rosenbluth J
1965 Aug;26(2):579-591, Journal of cell biology
— id: 8711, year: 1965, vol: 26, page: 579, stat: Journal Article,