Date of Award

2023

Degree Name

Biomedical Sciences

College

Joan C. Edwards School of Medicine

Type of Degree

Ph.D.

Document Type

Dissertation

First Advisor

Dr. Mary-Louise Risher, Committee Chairperson

Second Advisor

Dr. Richard Egleton

Third Advisor

Dr. Brandon Henderson

Fourth Advisor

Dr. Chris Risher

Fifth Advisor

Dr. Nadja Spitzer

Abstract

Alcohol is the third leading cause of preventable death in the United States and has substantial social and economic burdens. Excessive alcohol consumption in the form of binge drinking is highly prevalent among adolescents and emerging adults. Binge drinking is a form of excessive drinking, defined as consuming enough alcohol on a single occasion to result in blood alcohol concentrations above 0.08%. Approximately 55% of full-time college students aged 18- 22 years old have reported consuming alcohol in a binge manner. Furthermore, studies have shown that approximately 20% of college students meet the criteria for an alcohol use disorder (AUD). These statistics are concerning as this period of increased proclivity to participate in binge-type alcohol consumption overlaps with the critical period of adolescent development. During adolescence, the central nervous system (CNS) is undergoing a stage of neurodevelopment in which regions of the brain, such as the prefrontal cortex (PFC) and the hippocampus, which are critical for learning and higher cognitive development, continue to undergo refinement and maturation. Consuming alcohol during early adolescence results in long-term deficits in cognitive function and an increased risk of developing an AUD later in life. There has been a concerted effort to understand the direct contributions of adolescent binge drinking to long-lasting changes in neuronal structure, function, and subsequent cognitive changes that may be associated with the emergence of neuropsychiatric disorders and addiction. However, non-neuronal cells’ contribution to alcohol-induced neuronal dysfunction is just beginning to be elucidated. Astrocytes are highly complex non-neuronal glial cells that serve in developing, refining, and maintaining the CNS. Furthermore, very few studies are dedicated to investigating potential sex differences in the effects of adolescent alcohol exposure on astrocytes. Parallels in findings in human clinical data and laboratory studies using rodent models have allowed our lab and others to use a rat model of adolescent intermittent binge ethanol (EtOH) exposure (AIE) to begin to identify the roles of astrocytes in AIE-induced long-term neuronal dysfunction across multiple brain regions in males and females. This dissertation encompasses the investigation of 1) the short- and long-term effects of AIE on astrocyte morphology and astrocyte-synaptic interactions across multiple subregions of the male PFC, 2) the long-term effects of AIE on astrocyte morphology, astrocyte-synaptic interactions, and astrocyte function at the synapse in the female hippocampus, and 3) the short- and long-term effects of AIE on astrocyte morphology, astrocyte-synaptic proximity and interactions, subsequent astrocyte function at the synapse and hippocampal behaviors in male rodents. Overall, this dissertation aims to fill in gaps of knowledge by identifying how AIE impacts astrocytes across different brain regions undergoing adolescent neurodevelopment and how these effects may vary between sexes.

Subject(s)

Drinking of alcoholic beverages – Health aspects – Research.

Teenagers – Alcohol use – Health aspects – Research.

Astrocytes – Alcohol use – health aspects – Research.

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