Date of Award

2018

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Neuroscience

Abstract

Recent advances in genomics research have revealed that preconception behaviors and experiences of mothers and fathers, including diet, environmental toxicants, and drug abuse, can impact future offspring through epigenetic mechanisms. This means that the risky behaviors of young people, such as the extremely popular practice of binge drinking, have potentially far-reaching consequences for generations to come. While there has been considerable research into fetal alcohol exposure and parental alcoholism, there has yet to be sufficient investigation into the mechanism of epigenetic inheritance or the functional consequences of parental preconception binge pattern alcohol abuse. The hypothesis tested herein is that parental preconception alcohol exposure can impact offspring through epigenetic inheritance of DNA methylation patterns in the hypothalamus, leading to impaired hypothalamic function during development and a predisposition to neurodegeneration. This dissertation reveals that 1) male offspring of both maternal and paternal preconception alcohol exposure have genome-wide changes in methylation patterns in the hypothalamus, 2) offspring have altered hypothalamic function resulting in modest phenotypic and behavioral changes lasting through pubertal development, 3) parental preconception alcohol exposure does not confer advantages to offspring for improved alcohol metabolism, and 4) lipid homeostasis may be disrupted in the brain of alcohol-naïve offspring following parental alcohol exposure, as well in the brain of the parents themselves. These results suggest that parental preconception alcohol exposure confers maladaptive epigenetic traits to first generation offspring.

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