Mariko Saito, PhD

My research focuses on elucidating the mechanisms behind alcohol-induced acute damage in the developing brain, which leads to fetal alcohol spectrum disorder, a primary cause of intellectual disability. I also investigate the consequent long-lasting biochemical, anatomical, and electrophysiological changes that cause abnormal behavior in adult mice.

Our work in mouse models has led to several novel findings:

• Alcohol alters lipid metabolism in the developing brain. These changes include elevations in ceramide, which is implicated in alcohol-induced apoptosis, and in GM2 gangliosides, which are implicated in alcohol-induced glial cell activation.
• Alcohol inhibits AKT, AMP-activated protein kinase (AMPK), and activated glycogen synthase kinase 3 beta (GSK3B) in the developing brain, resulting in increased phosphorylation of tau.
• Alcohol exposure in neonatal mice induces acute neurodegeneration and glial cell activation, as well as long-lasting anatomical, electrophysiological, and behavioral changes. Co-treatment with lithium, a GSK3B inhibitor, reverses these short- and long-term effects of alcohol exposure during development.
• The major long-term cellular change induced by alcohol exposure during development is a specific decrease in parvalbumin interneurons, which is also observed in other developmental disorders.
• Fragmented sleep, one of the long-lasting behavioral changes caused by alcohol exposure during development, may contribute to cognitive dysfunction.