Degree

Doctor of Philosophy (PhD)

Department

comparative biomedical sciences

Document Type

Dissertation

Abstract

Arsenic is the highest-ranked substance on the Agency for Toxic Substances and Diseases Registry (ATSDR) Priority List, with an estimated 200 million people exposed worldwide. Reports of elevated developmental exposure levels, coupled with arsenic’s ability to cross the blood brain barrier and induce neurobehavioral alterations, suggest a potential role in the onset or progression of stress-related disorders. However, the neurobiological mechanisms underlying arsenic-induced neurobehavioral alterations remain poorly understood—presenting a gap that hinders the mitigation and treatment of these disorders. Given evidence that arsenic alters glucocorticoids (GC) signaling, a major output of the hypothalamic-pituitary-adrenal (HPA) stress axis, we hypothesize that arsenic disrupts stress behavior by impairing normal HPA axis function. Accordingly, the overarching objective of this dissertation was to define the role of developmental arsenic exposure as a risk factor for stress-related disorders and determine how HPA axis dysfunction contributes to these behavioral alterations. To achieve this objective, we pursued three aims: (1) establish a zebrafish neurobehavioral testing platform incorporating multiple sensory stimuli to characterize stress behavioral phenotypes while accounting for sensorimotor confounders (Chapters 2 and 3); (2) apply this platform to investigate the effects of developmental arsenic exposure on stress behavior in larval zebrafish (Chapter 4); and (3) determine the role of HPA axis signaling in mediating arsenic-induced stress behavioral phenotypes (Chapter 5). Collectively, our findings strongly support developmental arsenic exposure as a driver of stress behavioral alterations and identify HPA axis dysfunction as a key mediator of these effects, providing mechanistic insight that may improve risk assessment and inform strategies to mitigate stress-related disorders.

Date

7-27-2026

Committee Chair

Ahmed Abdelmoneim

LSU Acknowledgement

1

LSU Accessibility Acknowledgment

1

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Available for download on Wednesday, July 16, 2031

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