Date of Award

5-2025

Document Type

Thesis

Degree Name

Master of Science (MS)

College/School

College of Science and Mathematics

Department/Program

Biology

Thesis Sponsor/Dissertation Chair/Project Chair

Christos Suriano

Committee Member

Jennifer Krumins

Committee Member

Carlos Molina

Abstract

Alcohol use disorder (AUD) and obesity are major public health concerns, contributing to more than 28 million deaths annually. Despite extensive research, the mechanisms underlying excessive alcohol and food consumption remain incompletely understood. Emerging evidence suggests that neuro-immune crosstalk plays a pivotal role in feeding and alcohol-induced behaviors, with inflammation as a key pathological hallmark. Toll-like receptors (TLRs), traditionally recognized for their role in innate immunity, have recently been implicated in modulating neural responses to ethanol. However, the mechanisms of how TLR signaling influences feeding and alcohol-related behaviors remain largely unknown. To address this gap, we leveraged Caenorhabditis elegans (C. elegans), which possesses a single TLR homolog, TOL-1, to investigate its role in feeding and ethanol-induced behaviors. Our findings demonstrate that TOL-1 signaling in neurons modulates feeding in a hunger-state-dependent manner, promotes turning behaviors to avoid noxious stimuli, enhances survival during exposure to high doses of ethanol by limiting oxidative stress, mitigates ethanol-induced intoxication, and suppresses ethanol-seeking behavior. Additionally, TOL-1 facilitates an easily extinguished learned aversion to ethanol, highlighting its involvement in adaptive behavioral responses. Together, these results reveal a previously unrecognized role for TLRs in regulating ingestion behaviors beyond immune defense and pathogen avoidance. By elucidating TOL-1’s function in C. elegans, this study provides insights into conserved molecular mechanisms underlying alcohol consumption and feeding behaviors. Understanding these interactions could inform novel therapeutic strategies targeting immune signaling pathways to mitigate excessive alcohol intake and metabolic dysfunction in higher organisms.

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