DOI
https://doi.org/10.25772/APSJ-HE14
Defense Date
2020
Document Type
Thesis
Degree Name
Master of Science
Department
Pharmacology & Toxicology
First Advisor
Jennifer Wolstenholme
Second Advisor
John Bigbee
Third Advisor
Laura Sim-Selley
Abstract
Binge drinking is the most lethal of drinking patterns, responsible for 77% of all U.S. alcohol misuse costs. Adolescents have increased sensitivity to ethanol’s rewarding properties and decreased sensitivity to ethanol’s aversive effects likely allowing for their increased binge drinking, as compared to adults. Ethanol consumption during adolescent neurodevelopment can lead to immediate and lasting neurobiological-consequences. We have previously shown that adolescent intermittent binge ethanol exposure decreases myelin-related gene expression in DBA/2J mice. Here, we hypothesize intermittent binge ethanol exposure in adolescent DBA/2J mice will decrease myelin protein expression in the prefrontal cortex (PFC) immediately following binge ethanol and this may persist into adulthood. Adolescent DBA/2J mice (PND 29-42) were intermittently dosed with 4g/kg ethanol or water through oral gavage. Markers of puberty onset and sexual maturation were tracked in males and females to assess if ethanol affects sexual development. To assess immediate and persistent effects of binge ethanol exposure, PFC was harvested in adolescence (PND 43) and adulthood (PND 66), cryosectioned and immunostained for myelin basic protein (MBP). Western blotting was conducted to provide a complementary semi-quantitative technique to further assess the effects of binge ethanol exposure on MBP and PLP protein expression. We found that binge ethanol did not significantly alter myelin protein expression, specifically for MBP and PLP. However, we noted that ethanol males displayed a slight trend towards decreased protein expression in adolescence. In addition, we found that adult control females had significantly more PLP protein expression as compared to control males in adulthood (PND 84). Thus, we added to our previous mRNA findings with a potential trend towards decreased MBP and PLP expression in ethanol males at the protein level and found sex differences. Further work to verify these trends is needed. Together, these findings help elucidate the potential effects of ethanol on white matter integrity in the PFC and bolster our earlier mRNA findings at the protein level, which may provide the framework for future studies to uncover a mechanism by which ethanol acts to disrupt white matter.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
5-15-2020