Ethanol-Induced Reactive Astrocytes and Recovery

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Project Summary Individuals with Alcohol Use Disorder (AUD) frequently experience cognitive deficits, which are believed to be related to alcohol-induced corticolimbic damage. Following abstinence from alcohol, individuals can recover some function, but the mechanism behind this process is poorly understood. Astrocytes, glial cells which perform numerous important homeostatic functions in the brain, exhibit phenotypic changes following exposure to ethanol in animal models. Astrocyte reactivity is highly pathology specific, and many of the characteristics of this reactivity have not been studied in detail using an animal model of alcohol dependence and neurodegeneration. Evidence collected thus far indicates that this reactivity results in changes to astrocyte structure and precedes a burst in neurogenesis seen in abstinence. Given the role of astrocytes in releasing neurotransmitters and growth factors, these alcohol-induced reactive astrocytes might play an important role in recovery from AUD. This project will utilize two aims to first describe the phenotype of these astrocytes, and then probe a possible mechanism for their role in recovery. In both aims, rats will be exposed to ethanol, in a model which mimics the intoxication, dependence, and neurodegeneration experienced by humans with AUD. In Aim 1, a multi-faceted approach will be utilized to describe astrocyte morphology, proteins of interest that may be involved in recovery, and gene expression. In Aim 2, a pharmacologic approach will be taken to modulate glutamate signaling in astrocytes, to understand how this facet of phenotypic change may affect neurogenesis and recovery from AUD. Training: This project will significantly advance the training goals of the applicant by providing instruction in advanced scientific techniques and professional development to help the applicant achieve his career goal of becoming an independent researcher. Training in data science classes, accompanied by faculty mentorship, will assist with analyzing large data sets needed to complete this project. Professional development training will include undergraduate mentoring, presentation of science both internally and at conferences, research conduct training, and career development opportunities.