Author ORCID Identifier

https://orcid.org/0009-0003-8498-8908

Document Type

Thesis

Date of Award

Spring 5-2023

Keywords

alcohol use disorder, medial prefrontal cortex, sex differences, alcohol, synaptic-associated genes, neurotransmission

Degree Name

Integrative Neuroscience (BS)

Department

Neuroscience

First Advisor

Dr. Florence P. Varodayan

Series

Science and Mathematics

Subject Heading(s)

Alcoholism -- Complications ; Alcohol -- Physiological effect ; Brain -- Effect of drugs on

Abstract

Alcohol use disorder (AUD) is a serious chronic brain disease; in 2021 there were ~29.5 million people in the U.S. diagnosed with AUD. Individuals with AUD often show cognitive impairment such as risky decision-making, difficulties with impulse control, and working memory deficits. This impairment is associated with structural and functional changes in the prefrontal cortex (PFC), an extensively interconnected region of the frontal lobe involved in executive control of goal-directed behaviors. Chronic alcohol exposure in rodents has been seen to cause deficits in performance in behavioral tasks which assess mPFC function such as working memory and behavioral flexibility. It is thought that the remodeling of mPFC synapses contributes to alcoholrelated cognitive impairment, but it is not known which specific pathways and genes are responsible for alcohol's long-term effects. Given that synaptic transmission is likely an important contributor to the development of these long-term cognitive deficits, it is surprising that relatively little is known about how alcohol affects expression of the synaptic vesicle fusion machinery in males and females. Thus, the purpose of this study was to investigate how acute and repeated alcohol exposure modify the gene expression of synaptic vesicle-associated proteins, including HSF1, VAMP1, VAMP2, and Syt1 in the mPFC of male and female mice Through qPCR, we found significant sex and alcohol exposure differences in synaptic gene expression. In males, Vamp1 expression increased after acute alcohol exposure and decreased after repeated alcohol exposure. In females, Vamp2 expression increased after acute and repeated ethanol exposure and Hsf1 expression increased after repeated ethanol exposure. These findings suggest that ethanol differentially induces changes in the expression of synaptic genes in male and female mPFC, which likely impacts neurotransmission through changes in the synaptic vesicle fusion machinery. Additionally, this suggests that there is a compensatory mechanism to counteract the effects of multiple ethanol exposures, which is present in the male mPFC but not in the female mPFC. Therefore, future studies should investigate potential sex differences through a systems biology approach by investigating how alcohol can regulate expression and function of postsynaptic GABA and glutamate receptors, as well as GABA and glutamate release.

Creative Commons License

Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License
This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 4.0 International License.

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