Date of Award

Spring 5-11-2015

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Neuroscience Institute

First Advisor

Nancy G. Forger

Second Advisor

Anne Z. Murphy

Third Advisor

Laura Carruth

Fourth Advisor

Erin Tone

Abstract

Stress-related mood disorders, such as anxiety and depression, are the most common psychiatric conditions, occurring with a lifetime risk of 15-20%. Women are twice as likely to develop anxiety and depression than men, and this sex difference emerges during puberty. Exposure to abuse or maltreatment during early life increases mood disorder susceptibility, suggesting that females may be especially sensitive to long-lasting, negative effects of early-life stress. While the female-bias in mood disorders is one of the most robust sex differences in psychiatry, the origin of this difference remains unknown. Sexually dimorphic processing of stressors by the adolescent brain, or the sex-specific expression of stress-related neural substrates, may be mechanisms by which stress-related mood disorders are more prominent in females. We developed a novel animal model of early-life adversity, Juvenile Social Subjugation (JSS), to test the effect of chronic adolescent social stress on mood disorder-like pathology in adulthood. This dissertation addressed the following research questions: (1) Does chronic JSS induce sex-specific anxiety and depression-like behaviors and HPA axis dysfunction in adulthood? (2) Is JSS differentially processed by the male and female adolescent brain? (3) Is the corticotropin-releasing factor receptor (CRF) system sex-specifically expressed across development? Together our data point to regional sex differences in neuronal activation and CRF receptor expression in the brain as potential mechanisms by which stressors such as JSS induce sex-specific mood disorder-like behavior in adulthood.

Share

COinS