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Author ORCID Identifier

https://orcid.org/0000-0002-7186-7248

AccessType

Open Access Dissertation

Document Type

dissertation

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Neuroscience and Behavior

Year Degree Awarded

2022

Month Degree Awarded

February

First Advisor

Heather N. Richardson

Subject Categories

Behavioral Neurobiology

Abstract

Alcohol binge drinking during adolescence is associated with higher risk of developing alcohol use disorders later in life. Alcohol can lead to decreased white matter volume, myelin damage, and neuroinflammation in animal models of adolescent binge alcohol exposure. These deficits in turn are associated with cognitive disfunctions that are long-lasting and could contribute to alcohol abuse and alcoholism later in life. Importantly, human males are more likely to develop alcohol use disorders than females, thus the mechanisms underlying this might be different between the sexes. Understanding how alcohol impacts the developing adolescent brain can help us identify molecular and cellular pathways to target for therapeutic intervention. Here we sought to determine whether males and females are affected differently by voluntary alcohol drinking using an operant self-administration paradigm, and whether this level of alcohol exposure is enough to elicit similar inflammatory responses as those seen in chronic models of binge alcohol exposure. We found that alcohol had a negative impact on myelin microstructure in both males and females, however, overall myelinated fiber density was significantly reduced only in males, suggesting impaired remyelination. Similarly, males appeared to have a more robust inflammatory response than females, as indicated by upregulation of the gene that encodes for Toll-like receptor 4 (Tlr4) after alcohol drinking. While females did have an inflammatory response to alcohol, there was no change in the levels of Tlr4, and this was not due to differing circulating levels of pubertal hormones, as ovariectomized females also exhibited a similar attenuated response to alcohol. Taken together, this suggests that males might be more vulnerable to the effects of alcohol pre-pubertally, partly due to a more robust inflammatory response to alcohol, possibly related to sex differences in innate and adaptive immunity.

DOI

https://doi.org/10.7275/27115268.0

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