Regulation of gray matter myelination by adolescent binge ethanol treatment

Ohio State University, Columbus OH

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Abstract

Project Summary Chronic ethanol consumption has adverse effects on higher brain functions. The hippocampus, which plays important roles in learning, memory and anxiety, is known as one of the most sensitive targets for the neurotoxic effects of ethanol. Adolescents binge drink more than any other age group. Adolescents with alcohol use disorders develop deficits in executive functioning, learning and memory, but the pathogenic mechanisms remain poorly understood. Adolescence is a developmental period associated with maturation of cognitive ability, personality, and frontal cortical executive functions. This coincides with gray matter myelination. Gray matter demyelination can be induced by early life stress (e.g. social isolation), and is implicated in a number of conditions, such as Alzheimer's disease, multiple sclerosis, temporal lobe epilepsy, and psychotic disorders. It is known that chronic ethanol consumption correlates with demyelination and cognitive deficits. Based on our preliminary data, we propose to test an original hypothesis that binge-like ethanol exposure in adolescence damages brain function, in part, through gray matter demyelination, and this demyelination can persist into adulthood and be blocked by antioxidant treatment. We will use a well- establish animal model that has been extensively validated in the field, combined with behavioral and morphological studies. We will determine (1) alterations of behavior and gray matter myelination following binge-like ethanol exposure in adolescent and adult mice, and (2) effects of antioxidant treatment on ethanol- induced demyelination. This exploratory project will allow my laboratory to establish in vivo animal models to systematically study the role of gray matter demyelination following adolescent binge ethanol exposure. These studies may identify an effective antioxidative treatment that can protect myelin from the damage induced by adolescent ethanol exposure.