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The Nathan S. Kline Institute for Psychiatric Research

Neurochemistry

Mariko Saito Lab

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Alcohol induces damage in the developing brain, leading to fetal alcohol spectrum disorders (FASD), a primary cause of intellectual disability. Using mouse models of FASD, the focus of our laboratory is to study mechanisms underlying alcohol-induced acute damage in the developing brain as well as long-lasting cellular, anatomical, and electrophysiological changes that culminate in abnormal behavior in adult mice. One of our major goals is to elucidate roles of cellular sphingolipids in neurodegeneration and glial activation observed in the developing brain exposed to ethanol during the third trimester-equivalent period. In collaboration with Dr. Mitsuo Saito (Psychopharmacology), our studies include cellular and subcelluar lipid analyses, gene expression profiling, and the use of transgenic mice.

Effects of Alcohol on the Developing Brain

Another major goal is to understand how alcohol-induced acute changes in the developing brain lead to long-lasting cellular, electrophysiological, and behavioral abnormalities in adult animals. Specifically, in collaboration with Dr. Wilson (Emotional Brain Institute) and Dr. Smiley (Schizophrenia Research), the team studies how acute neurodegeneration and glial activation causes long-term GABAergic neuron deficits, and how the GABAergic neuron deficits are related to electrophysiological and behavioral changes including abnormal slow wave sleep patterns and deficits in spatial memory performance. These studies include stereological cell counting, and electrophysiological and behavioral experiments using wild-type and transgenic mice such as Gad67-GFP knock-in mice.

Exosome Studies

Also, in collaborative studies with Dr. Levy (Center for Dementia Research), Dr. Sershen (Neurochemistry), and Dr. Mitsuo Saito, we are studying the effects of ethanol and cocaine on lipid profiles of brain exosomes, because exosomes may modify the toxicity and other effects of ethanol and cocaine by regulating the expression of specific proteins and lipids of neural cells.