Biomedical Sciences ETDs

Publication Date

Summer 7-28-2026

Abstract

Fetal alcohol spectrum disorder (FASD) results from prenatal alcohol exposure (PAE) and is linked to development of mood disorders, which in turn are driven by dysregulation of the sympathetic nervous system, the neuroendocrine hypothalamic-pituitary-adrenal (HPA) axis, and the central nervous system (CNS) neuroimmune response to stressors. PAE alters brain glial activation and proinflammatory cytokine expression through secondary challenges such as psychological stressors. The goals of the experiments presented in this dissertation were to 1) examine peripheral glucocorticoid receptor function following mild acute stress in adult PAE offspring, 2) characterize a sensitized cytokine stress response in the hippocampus, medial prefrontal cortex, and hypothalamus of PAE adults after mild stress, and 3) characterize the behavioral response of PAE adults, following mild acute stress in adulthood or stress in adolescence. We found that a single, mild stress in adulthood does not alter the peripheral glucocorticoid response in PAE offspring, while mRNA expression of inflammatory factors in the male hippocampus and the female hypothalamus are vulnerable to the effects of such a stress. PAE adults with a history of stress during adolescence show increased anxiety-like behaviors alongside increased levels of expression of CXCL1 and IL-1B in the hippocampus. These experiments have revealed important characterizations of sex- and region-specific differences in cytokine expression that may contribute to the development of anxiety-like behaviors in adults with PAE, and will inform future studies that will investigate the mechanisms behind these altered levels of cytokines.

Keywords

Prenatal alcohol exposure, neuroimmune, stress, HPA, cytokines, anxiety

Document Type

Dissertation

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Doctoral

Department Name

Biomedical Sciences Graduate Program

First Committee Member (Chair)

Dr. Fernando Valenzuela

Second Committee Member

Dr. Erin Milligan

Third Committee Member

Dr. Jonathan Brigman

Fourth Committee Member

Dr. Amy Gardiner

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