ORCID

https://orcid.org/0009-0000-0087-8778

Date of Award

Summer 2025

Language

English

Embargo Period

7-9-2025

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

College/School/Department

Department of Psychology

Program

Behavioral Neuroscience

First Advisor

Damian Zuloaga

Committee Members

Andrew Poulos, Christine Wagner

Keywords

stress, sex differences, mice, androgens, endocrinology

Subject Categories

Behavioral Neurobiology | Molecular and Cellular Neuroscience

Abstract

Sex differences in the morphology of the brain are thought to underlie the sex differences we see in anxiety and depression, where women are twice as likely to be diagnosed when compared to men. Stress, or a disruption to homeostasis, can exacerbate these mood disorders. Corticotropin releasing factor (CRF), and its receptors, play an important role in regulating the stress response. Binding of CRF with CRFR2 has been shown to reduce behavioral and neuroendocrine stress responses, yet whether there are sex differences in CRFR2 expressing neurons and stress-induced activation of these neurons in mice is unknown, in part due to a lack of specific antibodies for CRFR2. Here, we use transgenic reporter mice (CRFR2-Cretdtom) and subject them to both an acute stressor and a chronic stress paradigm, in order to assess sex differences in CRFR2 cell number and the stress activation of CRFR2 cells.

Higher levels of androgens in males, acting through androgen receptors (AR), provide a protective mechanism against the development of mood disorders. Androgens regulate the responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis as well as anxiety- and depressive-like behaviors. Therefore, we investigated whether CRFR2 expressing neurons co-express AR, and if a sex difference exists in co-expression. We also determined whether circulating androgens regulate CRFR2 levels or the stress activation of CRFR2 neurons, by gonadectomy or sham-operating male CRFR2-Cretdtom mice.

The paraventricular nucleus (PVN) of the hypothalamus is a critical component of the HPA axis and driver of stress-related behaviors. It is known that CRFR2 is expressed in the PVN, yet little is known about the phenotype of these neurons or the behaviors they might govern. Here, we investigated the chemical composition of PVN CRFR2 cells with several colocalization studies and looked at where these cells projected centrally and peripherally with two tracing studies. Further, we investigated the impact of ablating PVN CRFR2 neurons, which gives insight into the role that these cells play in governing anxiety-and depressive-like behaviors.

License

This work is licensed under the University at Albany Standard Author Agreement.

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