Helen M. Chao, Ph.D.

BDNF Val66Met variant and age of onset in schizophrenia
Chao, Helen M; Kao, Hung-Teh; Porton, Barbara
2008 Jun 5;147B(4):505-506, American journal of medical genetics. Part B, Neuropsychiatric genetics
Brain-derived neurotrophic factor (BDNF) has been advanced as a candidate gene for schizophrenia by virtue of its effects on neurotransmitter systems that are dysregulated in psychiatric disorder and its involvement in the response to antipsychotic drugs. The extensively examined BDNF gene Val66Met (or rs6265) variant has been associated with schizophrenia, and studies have linked this polymorphism to brain morphology, cognitive function, and psychiatric symptoms in schizophrenia. Moreover the BDNF Val66Met variant has been reported to be associated with age of onset in schizophrenia. Genotyping of African-American subjects with schizophrenia for five BDNF coding region single nucleotide polymorphisms revealed variance only at the Val66Met allele. The results of statistical analyses indicate a relationship between the BDNF Val66Met genotype and the ages of first psychiatric hospitalization and first schizophrenia symptoms
— id: 96165, year: 2008, vol: 147B, page: 505, stat: Journal Article,

Early involvement of synapsin III in neural progenitor cell development in the adult hippocampus
Kao, Hung-Teh; Li, Ping; Chao, Helen M; Janoschka, Stephen; Pham, Kara; Feng, Jian; Mcewen, Bruce S; Greengard, Paul; Pieribone, Vincent A; Porton, Barbara
2008 Apr 20;507(6):1860-1870, Journal of comparative neurology
Synapsin III is a synaptic vesicle-associated protein that is expressed in cells of the subgranular layer of the hippocampal dentate gyrus, a brain region known to sustain substantial levels of neurogenesis into adulthood. Here we tested the hypothesis that synapsin III plays a role in adult neurogenesis with synapsin III knockout and wild-type mice. Immunocytochemistry of the adult hippocampal dentate gyrus revealed that synapsin III colocalizes with markers of neural progenitor cell development (nestin, PSA-NCAM, NeuN, and Tuj1) but did not colocalize with markers of mitosis (Ki67 and PCNA). Because neurogenesis consists of a number of stages, the proliferation, survival, and differentiation of neural progenitor cells were systematically quantitated in the hippocampal dentate gyrus of adult synapsin III knockout and wild-type mice. We found a 30% decrease in proliferation and a 55% increase in survival of neural progenitor cells in synapsin III knockout mice. We also observed a 6% increase in the number of neural progenitor cells that differentiated into neurons. No difference in the volume of the dentate gyrus was observed between synapsin III knockout and wild-type mice. Collectively, our results demonstrate a novel role for synapsin III in regulating the proliferation of neural progenitor cells in the adult hippocampal dentate gyrus. These findings suggest a distinct function for this synaptic vesicle protein, in addition to its role in neurotransmission
— id: 76467, year: 2008, vol: 507, page: 1860, stat: Journal Article,

Investigation of the phenylalanine hydroxylase gene and tardive dyskinesia
Richardson, Mary Ann; Chao, Helen M; Read, Laura L; Clelland, James D; Suckow, Raymond F
2006 Mar 5;141B(2):195-197, American journal of medical genetics. Part B, Neuropsychiatric genetics
Phenylketonuria (PKU), an inborn error of phenylalanine metabolism, has been shown to be a risk factor for tardive dyskinesia (TD). In male psychiatric patients there was a significant relationship between TD and measures of plasma phenylalanine following ingestion of a standardized phenylalanine dose that was indicative of higher brain availability of phenylalanine in patients with TD. In addition, a medical food formulation consisting of branched chain amino acids, which compete with phenylalanine for transport across the blood-brain barrier, has been demonstrated to be an efficacious treatment for TD. Cumulatively these findings suggested that TD was related to phenylalanine metabolism and thus that sequence variants in the gene for phenylalanine hydroxylase (PAH), the rate-limiting enzyme in the catabolism of phenylalanine, could be associated with TD susceptibility. Genetic screening of PAH in a group of 123 psychiatric patients revealed ten sequence polymorphisms and two mutations, but none appeared to be a significant risk factor for TD
— id: 94379, year: 2006, vol: 141B, page: 195, stat: Journal Article,

Evidence for a tetrahydrobiopterin deficit in schizophrenia
Richardson, M A; Read, Laura L; Taylor Clelland, Catherine L; Reilly, Margaret A; Chao, Helen M; Guynn, Robert W; Suckow, Raymond F; Clelland, James D
2005 ;52(4):190-201, Neuropsychobiology
Tetrahydrobiopterin (BH(4)) is a vital cofactor maintaining availability of the amine neurotransmitters [dopamine (DA), noradrenaline (NA), and serotonin (5-HT)], regulating the synthesis of nitric oxide (NO) by nitric oxide synthase (NOS), and stimulating and modulating the glutamatergic system (directly and indirectly). These BH(4) properties and their potential relevance to schizophrenia led us to investigate the hypothesis of a study group (healthy controls, n=37; schizophrenics, n=154) effect on fasting plasma total biopterin levels (a measure of BH(4)). Study analysis showed a highly significant deficit of total biopterins for the schizophrenic sample after partialling out the effects of potential confounds of gender, age, ethnicity, neuroleptic use history and dose of current use, 24-hour dietary phenylalanine/protein ratio (a dietary variable relevant to BH(4) synthesis), and plasma phenylalanine (which stimulates BH(4) synthesis). A mean decrement of 34% in plasma total biopterins for schizophrenics from control values supports clinical relevance for the finding. In a subsample (21 controls and 23 schizophrenics), sequence analysis was done of the GTP cyclohydrolase I feedback regulatory gene and no mutations were found in the coding region of the gene. A deficiency of BH(4) could lead to hypofunction of the systems of DA, NA, 5-HT, NOS/NO, and glutamate, all of which have been independently implicated in schizophrenia psychopathology. Further, evidence has been accumulating which implicates the critical interdependence of these neurotransmitter systems in schizophrenia; this concept, along with the present study finding of a biopterin deficit, suggests that further study of the BH(4) system in schizophrenia is warranted and desirable
— id: 59357, year: 2005, vol: 52, page: 190, stat: Journal Article,

Branched Chain Amino Acid Treatment of Tardive Dyskinesia in Children and Adolescents
Richardson, Mary Ann; Small, Arthur M; Read, Laura L; Chao, Helen M; Clelland, James D
2004 Jan;65(1):92-96, Journal of clinical psychiatry
BACKGROUND: A series of studies had demonstrated that deficient clearance of the large neutral amino acid phenylalanine was associated with tardive dyskinesia (TD), that the administration of the branched chain amino acids (BCAA) significantly decreased TD symptoms over placebo, and that the observed TD symptom reduction was significantly correlated with a diminished availability of phenylalanine to the brain of adult men with psychosis. As part of an initiative by the National Institute of Mental Health to expand the testing of treatments that were successful in adults to children and adolescents, the present pilot study was undertaken to test whether the BCAA would also reduce TD symptoms in children and adolescents. A 2-week trial of the BCAA was thus conducted in 6 children and adolescents (age range, 10.5-16.5 years) for the treatment of TD symptoms. METHOD: A clinical diagnosis of TD was made in all subjects on the basis of a global score derived from the Simpson Abbreviated Dyskinesia Rating Scale. Subjects were videotaped for TD evaluation at baseline and after 1 and 2 weeks of BCAA treatment given in the form of a drink administered 3 times daily. TD symptom change over the trial period was evaluated by researchers blinded to the treatment status of the evaluation. RESULTS: TD symptom decreases were substantial in 5 of the 6 participants, ranging from 40% to 65%. Two of the subjects received an additional course of treatment, and further reductions in TD symptoms over those seen in the 2-week trial were observed. CONCLUSION: The substantial symptom decrease and tolerability observed suggest the use of the BCAA formulation for the treatment of TD in children and adolescents and warrant further large-scale studies
— id: 42016, year: 2004, vol: 65, page: 92, stat: Journal Article,

Efficacy of the branched-chain amino acids in the treatment of tardive dyskinesia in men
Richardson, Mary Ann; Bevans, Margaret L; Read, Laura L; Chao, Helen M; Clelland, James D; Suckow, Raymond F; Maher, Timothy J; Citrome, Leslie
2003 Jun;160(6):1117-1124, American journal of psychiatry
OBJECTIVE: The efficacy of the branched-chain amino acids in the treatment of tardive dyskinesia in men with psychiatric disorders was tested. METHOD: Public-sector psychiatric patients with long histories of antipsychotic treatment and presumably long-standing tardive dyskinesia were randomly assigned to receive branched-chain amino acids or placebo. Treatment frequency was three times a day, 7 days a week for 3 weeks. The efficacy measure was a frequency count of videotaped tardive dyskinesia movements. RESULTS: A robust and highly significant difference was observed between patients who received high-dose branched-chain amino acids (222 mg/kg of body weight t.i.d.) (N=18) and those who received placebo (N=18) in the percent change in tardive dyskinesia symptoms from baseline to the end of the 3-week trial. Significant and marked differences were seen between the two groups at the >/=30% and >/=60% levels of decrease in tardive dyskinesia symptoms. No clinically significant differences were seen between the pre- and posttrial results of physical examinations and laboratory screening tests. Minimal gastrointestinal symptoms occurred during the trial. The reduction in tardive dyskinesia symptoms in the amino acids group was not related to changes in antipsychotic and glucose plasma levels. A mechanism of response related to decreased amine neurotransmitter synthesis was suggested by the significant positive correlations observed between decreases in tardive dyskinesia symptoms and decreases in aromatic amino acid plasma concentrations over the course of the trial. CONCLUSIONS: Branched-chain amino acids constitute a novel, safe treatment for tardive dyskinesia, with a strong potential for providing significant improvement in the diseased physiognomy of the afflicted person
— id: 38120, year: 2003, vol: 160, page: 1117, stat: Journal Article,

Phenylalanine hydroxylase gene in psychiatric patients: screening and functional assay of mutations
Richardson, Mary Ann; Read, Laura L; Clelland, James D; Chao, Helen M; Reilly, Margaret A; Romstad, Anne; Suckow, Raymond F
2003 Mar 15;53(6):543-553, Biological psychiatry
Reports relating phenylalanine kinetics and metabolism to psychiatric disorders led us to undertake the comprehensive screening of the phenylalanine hydroxylase (PAH) coding region and functional testing of discovered mutations in a sample of psychiatric patients and healthy control subjects.Genomic DNA from psychiatric patients and control subjects was assayed for sequence variants in all PAH coding regions and splice junctions. In vivo functional analysis of mutations was conducted by assessing the kinetics and conversion to tyrosine of a standardized phenylalanine dose and by measuring fasting pterin levels.A known missense mutation was observed in a schizoaffective subject, and a novel missense mutation was discovered in four subjects with schizophrenia and one normal subject. The schizoaffective patient heterozygous for the known A403V mutation showed the lowest rate of phenylalanine kinetics and lowest conversion to tyrosine in the patient sample. The four schizophrenic patients heterozygous for the novel K274E mutation showed significantly decreased phenylalanine kinetics, reduced conversion to tyrosine, and increased synthesis of the PAH cofactor tetrahydrobiopterin compared with schizophrenic subjects without the mutation.The study findings suggest that larger scale studies are warranted to test the relationship of the PAH genotype with a psychiatric phenotype
— id: 34147, year: 2003, vol: 53, page: 543, stat: Journal Article,

Aromatic amino acid hydroxylase genes and schizophrenia
Chao, Helen M; Richardson, Mary Ann
2002 Aug 8;114(6):626-630, American journal of medical genetics
Phenylalanine hydroxylase (PAH), which catalyzes the conversion of phenylalanine to tyrosine, shares physical, structural and catalytic properties with tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) that catalyze the rate-limiting steps in the biosynthesis of the neurotransmitters dopamine, noradrenaline, and serotonin. Because these neurotransmitter systems have all been implicated in the pathophysiology of schizophrenia, the aromatic amino acid hydroxylases are among the likely candidates for genes associated with schizophrenia. A mutation in the functionally critical tetrahydrobiopterin cofactor binding domain of the PAH gene had been identified in African-American patients with the diagnosis of schizophrenia, and biochemical analyses suggested that this mutation has physiological consequences related to amine neurotransmitter function. DNA sequencing of the highly conserved cofactor binding domain of the PAH, TH, and TPH genes in African-American subjects with schizophrenia and unrelated, never mentally ill subjects from the NIMH Schizophrenia Genetics Initiative, was undertaken to assess the concordance of mutant genotype with psychiatric phenotype. The K274E mutation was observed in the PAH gene cofactor binding domain, and several polymorphisms were identified in adjacent intronic regions of the PAH, TH, and TPH genes. All of the genetic variants observed were represented in the schizophrenia group and in the never mentally ill group. Genetic evaluation of the family members of subjects with the PAH K274E mutation showed that all individuals with the K274E mutation also exhibited the PAH L321L polymorphism in the catalytic domain of the PAH enzyme
— id: 34148, year: 2002, vol: 114, page: 626, stat: Journal Article,

Regulation of glucocorticoid receptor and mineralocorticoid receptor messenger ribonucleic acids by selective agonists in the rat hippocampus
Chao HM; Ma LY; McEwen BS; Sakai RR
1998 Apr;139(4):1810-1814, Endocrinology
Adrenal steroids can have prodigious effects on the structure, function, and survival of hippocampal neurons. In the rat hippocampus, the actions of adrenal steroids are mediated by two receptor types, the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). Using in situ hybridization, we have examined the regulation of the messenger RNAs (mRNAs) encoding the glucocorticoid and mineralocorticoid receptors, by aldosterone, which acts selectively through MR, and by RU28362, which acts selectively through GR. Our results demonstrate that there is autoregulation of each receptor subtype, such that activation of GR regulates GR mRNA levels and MR activation regulates MR mRNA expression. In addition, there is evidence that aldosterone, acting through MR, can affect the expression of GR mRNA. The extent to which a specific agonist can produce a significant change in the expression of a particular steroid receptor mRNA varies between the different subfields of the hippocampus
— id: 34150, year: 1998, vol: 139, page: 1810, stat: Journal Article,

Adrenal steroid regulation of neurotrophic factor expression in the rat hippocampus
Chao HM; Sakai RR; Ma LY; McEwen BS
1998 Jul;139(7):3112-3118, Endocrinology
Adrenal steroids and neurotrophic factors are important modulators of neuronal plasticity, function, and survival in the rat hippocampus. Adrenal steroids act through two receptor subtypes, the glucocorticoid receptor (GR) and the mineralocorticoid receptor, and activation of each receptor subtype has distinct biochemical and physiological consequences. Adrenal steroids may exert their effects on neuronal structure and function through the regulation of expression of neurotrophic and growth-associated factors. We have examined adrenal steroid regulation of the neurotrophins brain-derived neurotrophic factor, neurotrophin-3, and basic fibroblast growth factor, as well as the growth associated protein GAP-43, through activation of GR or mineralocorticoid receptor with selective agonists. Our findings indicated that in CA2 pyramidal cells, adrenalectomy resulted in decreases in the levels of basic fibroblast growth factor and neurotrophin-3 messenger RNA, which were prevented by activation of mineralocorticoid but not glucocorticoid receptors. Adrenalectomy-induced increases in GAP-43 and brain-derived neurotrophic factor messenger RNA levels could be blocked by activation of glucocorticoid receptors in CA1, but not in CA3, pyramidal cells. Thus the extent to which adrenal steroids regulate hippocampal neurotrophic and growth-associated factors, appears to be dependent both on the adrenal steroid receptor subtype activated and on the hippocampal subregion examined
— id: 34149, year: 1998, vol: 139, page: 3112, stat: Journal Article,

Ginsenoside Rb1 regulates ChAT, NGF and trkA mRNA expression in the rat brain
Salim KN; McEwen BS; Chao HM
1997 Jul;47(1-2):177-182, Brain research. Molecular brain research
Ginsenoside Rb1 (Rb1), a saponin of North American ginseng (Panax quinquefolium L.), has been found to exert beneficial effects on memory and learning, putatively through its actions on the cholinergic system. In situ hybridization studies show that Rb1 increases the expression of choline acetyltransferase and trkA mRNAs in the basal forebrain and nerve growth factor mRNA in the hippocampus. Other neurotrophins (brain-derived neurotrophic factor, neurotrophin-3), genes encoding neuropeptides (preproenkephalin, preprotachykinin) and amyloid protein precursor were also studied, but no significant change was observed. These findings support the specificity of the effects of Rb1 on certain aspects of the cholinergic and neurotrophic systems
— id: 34151, year: 1997, vol: 47, page: 177, stat: Journal Article,

Stress and the brain: a paradoxical role for adrenal steroids
McEwen BS; Albeck D; Cameron H; Chao HM; Gould E; Hastings N; Kuroda Y; Luine V; Magarinos AM; McKittrick CR; et al.
1995 ;51(1-2):371-402, Vitamines & hormones
— id: 34152, year: 1995, vol: 51, page: 371, stat: Journal Article,

Glucocorticoids and the expression of mRNAs for neurotrophins, their receptors and GAP-43 in the rat hippocampus
Chao HM; McEwen BS
1994 Oct;26(1-2):271-276, Brain research. Molecular brain research
The genes encoding brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and basic fibroblast growth factor (bFGF) are all expressed in the adult rat hippocampus. The colocalization of the these factors with the receptors to which they bind, namely trkB, trkC and the bFGF receptor, respectively, suggests that in the hippocampus they may exert their putative protective and trophic effects through an autocrine mechanism. The morphology and survival of hippocampal neurons are also affected by glucocorticoids, which can act as transcriptional activators of gene expression. In this study we have used in situ hybridization to investigate the adrenal steroid regulation of the mRNAs encoding the neurotrophic factors BDNF, NT-3, and bFGF, their respective receptors, and the growth-associated protein GAP-43. After 7 days of adrenalectomy (ADX), there was an increase in the level of GAP-43 mRNA expression in the CA1 and CA3 pyramidal cell layers of the hippocampus, that was prevented by corticosterone replacement to the ADX animals. In the CA2 subregion, adrenalectomy resulted in a decrease in bFGF mRNA expression, that was reversed by steroid treatment. There was evidence for glucocorticoid modulation of the BDNF and NT-3 mRNAs in pyramidal cell layers and in the dentate gyrus, but not of the mRNAs encoding the trkB, trk C or bFGF receptors
— id: 34154, year: 1994, vol: 26, page: 271, stat: Journal Article,

The effects of aging and hormonal manipulation on amyloid precursor protein APP695 mRNA expression in the rat hippocampus
Chao HM; Spencer RL; Frankfurt M; McEwen BS
1994 Oct;6(5):517-521, Journal of neuroendocrinology
In the rat hippocampus, neuronal morphology and survival are profoundly affected by adrenal steroids, and synaptic plasticity can be modulated by the ovarian sex steroids estrogen and progesterone. beta-amyloid peptides, which accumulate in neuritic plaques and are derived from the amyloid precursor protein (APP), have been shown to be both trophic and toxic for hippocampal neurons. Of the various APP isoforms, APP695 is the predominant form found in rat brain and the APP695 mRNA is abundantly expressed in the hippocampus. In order to investigate the hypothesis that APP may serve as a mediator of the steroid effects, we have monitored the hippocampal expression of APP695 mRNA by in situ hybridization, with aging and with steroid manipulation. In aged female rats we observed a decrease in the level of APP695 mRNA relative to young female rats, while no such age difference was evident in male rats. Physiological, surgical and pharmacological manipulation of glucocorticoids appeared to have no effect on APP695 mRNA levels in the hippocampus. Treatment of young, ovariectomized female rats with estrogen and progesterone, resulted in an increase in hippocampal APP695 expression compared to untreated, ovariectomized controls
— id: 34153, year: 1994, vol: 6, page: 517, stat: Journal Article,

Resolving a mystery: progress in understanding the function of adrenal steroid receptors in hippocampus
McEwen BS; Cameron H; Chao HM; Gould E; Luine V; Magarinos AM; Pavlides C; Spencer RL; Watanabe Y; Woolley C
1994 ;100(1-2):149-155, Progress in brain research
— id: 34155, year: 1994, vol: 100, page: 149, stat: Journal Article,

THE EFFECT OF SOCIAL STRESS ON HIPPOCAMPAL GENE-EXPRESSION
CHAO, HM; BLANCHARD, DC; BLANCHARD, RJ; MCEWEN, BS; SAKAI, RR
1993 DEC ;4(6):543-548, Molecular & cellular neurosciences
— id: 34161, year: 1993, vol: 4, page: 543, stat: Journal Article,

DIURNAL REGULATION OF GLUCOCORTICOID RECEPTOR AND MINERALOCORTICOID RECEPTOR MESSENGER-RNAS IN RAT HIPPOCAMPUS
HERMAN, JP; WATSON, SJ; CHAO, HM; COIRINI, H; MCEWEN, BS
1993 APR ;4(2):181-190, Molecular & cellular neurosciences
— id: 34162, year: 1993, vol: 4, page: 181, stat: Journal Article,

Adrenal steroids and plasticity of hippocampal neurons: toward an understanding of underlying cellular and molecular mechanisms
McEwen BS; Cameron H; Chao HM; Gould E; Magarinos AM; Watanabe Y; Woolley CS
1993 Aug;13(4):457-482, Cellular & molecular neurobiology
— id: 34156, year: 1993, vol: 13, page: 457, stat: Journal Article,

THE EXPRESSION OF GROWTH-ASSOCIATED PROTEIN GAP-43 MESSENGER- RNA IN THE RAT HIPPOCAMPUS IN RESPONSE TO ADRENALECTOMY AND AGING
CHAO, HM; SPENCER, RL; SAKAI, RR; MCEWEN, BS
1992 DEC ;3(6):529-535, Molecular & cellular neurosciences
— id: 34163, year: 1992, vol: 3, page: 529, stat: Journal Article,

Paradoxical effects of adrenal steroids on the brain: protection versus degeneration
McEwen BS; Angulo J; Cameron H; Chao HM; Daniels D; Gannon MN; Gould E; Mendelson S; Sakai R; Spencer R; et al.
1992 Jan 15;31(2):177-199, Biological psychiatry
— id: 34157, year: 1992, vol: 31, page: 177, stat: Journal Article,

Glucocorticoid regulation of neuropeptide mRNAs in the rat striatum
Chao HM; McEwen BS
1991 Mar;9(4):307-311, Brain research. Molecular brain research
Expression of the preprotachykinin (PPT) mRNA and of the preproenkephalin (PPE) mRNA in the rat striatum has been assessed by in situ hybridization. The results demonstrate that the PPT mRNA is regulated by glucocorticoids such that adrenalectomized (ADX) animals replaced with corticosterone for 5 days expressed higher levels of the mRNA than ADX animals. The corticosterone-induced increase in striatal PPT mRNA was evident after 16 h, but not after 2 h, of corticosterone treatment of ADX animals. Elevation of circulating corticosterone levels in intact rats by acute restraint stress, or by corticosterone injection did not change the level of PPT mRNA in the striatum. In intact rats there was a diurnal variation in the level of striatal PPE mRNA expression; adrenalectomy resulted in a decrease in the mRNA level and did not abolish the diurnal variation in expression. The level of PPT mRNA in the striatum was also decreased in response to ADX, but there were no significant diurnal changes in the expression of the PPT mRNA either in the intact or in the ADX animals
— id: 34158, year: 1991, vol: 9, page: 307, stat: Journal Article,

Glucocorticoid regulation of preproenkephalin messenger ribonucleic acid in the rat striatum
Chao HM; McEwen BS
1990 Jun;126(6):3124-3130, Endocrinology
Glucocorticoids regulate the level of preproenkephalin mRNA expression in a number of cell systems. This study investigated the expression of preproenkephalin mRNA in the brain and its regulation by glucocorticoids in vivo. Two different methods for mRNA quantitation were employed. Total RNA isolated from dissected brain tissue was analyzed in an RNAse T2 protection assay. In addition, we have used in situ hybridization to brain sections to assess the expression of preproenkephalin mRNA. The results demonstrate that in the striatum the preproenkephalin mRNA is expressed at a high level and is regulated by glucocorticoids. There is a decrease in striatal preproenkephalin mRNA after adrenalectomy (ADX), and ADX animals replaced with corticosterone express higher levels of striatal preproenkephalin mRNA than ADX animals. By in situ hybridization we have determined that the corticosterone-induced increase in striatal preproenkephalin mRNA is evident after 16 h, but not after 2 h, of corticosterone replacement of ADX animals. Elevation of circulating corticosterone levels in intact rats by 2-3 h of restraint stress, a multiple daily stress regimen over 1-21 days, or corticosterone injection did not change the level of preproenkephalin mRNA in the striatum; however, a single 16-h restraint stress resulted in a decreased level of expression. In intact rats there was a diurnal variation in the level of striatal preproenkephalin mRNA expression; ADX resulted in a decrease in the mRNA level, but did not abolish the diurnal variation in expression. Thus, while there is clearly regulation of striatal preproenkephalin mRNA by glucocorticoids, our results provide evidence for regulation by nonglucocorticoid mechanisms as well
— id: 34159, year: 1990, vol: 126, page: 3124, stat: Journal Article,

Glucocorticoid and mineralocorticoid receptor mRNA expression in rat brain
Chao HM; Choo PH; McEwen BS
1989 Oct;50(4):365-371, Neuroendocrinology
In the rat brain, the binding of corticosterone is mediated through two receptor types, the type I receptor and the type II receptor, which are presumed to be encoded by genes designated as MR and GR, respectively. We have studied the regulation of these receptors by glucocorticoids, utilizing a cytosol receptor binding assay. In addition, we have employed molecular probes for the GR and the MR to measure receptor mRNAs. The level of type II receptor binding is uniform across several brain regions, as is the expression of GR (type II) mRNA. In contrast, type I receptor binding is concentrated in the hippocampus, and the MR (type I) mRNA similarly shows a higher level of expression in hippocampus than in the other brain regions studied. Removal of endogenous glucocorticoids by adrenalectomy (ADX) induces an increase, and corticosterone administration results in a decrease, in the level of type I and type II binding in the hippocampus; however, no significant changes in the MR (type I) or GR (type II) mRNA levels are seen with these treatments. The diurnal variation of serum corticosterone in intact rats is correlated with a circadian regulation of type I receptor binding in the hippocampus, while MR (type I) mRNA expression is unaffected. Thus, the changes in type I and type II receptor binding capacity elicited by differing steroid conditions cannot be attributed to modulation of the steady state levels of MR (type I) or GR (type II) mRNA
— id: 34160, year: 1989, vol: 50, page: 365, stat: Journal Article,