The Effect of Mild Blast Traumatic Brain Injury on the Sexually Dismorphic Stress Axis
Abstract
This dissertation focuses on elucidating the effect of mbTBI on the HPA axis to address the gap in mechanism behind the subsequent development of TBI-induced psychiatric disorders. We demonstrate that mbTBI resulted in sex-dependent alterations of the HPA axis after a 7-10 day recovery period. Males exposed to mbTBI had increased restraint-induced CORT, but decreased CRF activation in the PVN. Interestingly, females exhibited the opposite response, with decreased restraint-induced CORT and increased CRF activation in the PVN after mbTBI. mbTBI had no effect on genes involved in the peripheral HPA axis or feedback regulation (MR/GR). We identified an autonomic link to HPA axis dysregulation in females. Additionally, we sought to determine the mbTBI induced effect on the extrahypothalamic CRF system. mbTBI had no effect on limbic CRFR1 gene expression. We show that mbTBI had a sex dependent effect of limbic CRFR2 gene expression. Males exposed to mbTBI had decreased CRFR2 gene expression in the amygdala and anterior bed nucleus of the stria terminalis, while females had decreased expression in the dorsal hippocampus. Collectively, these findings demonstrate a sex-dependent disruption of stress regulation circuitries after mbTBI. These data suggest that males and females utilize different strategies to cope with mbTBI, highlighting the importance of developing targeted sex dependent treatments
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 14, 2018
- Accession Number
- AD1132074
Entities
People
- Ashley L Russell
Organizations
- Uniformed Services University of the Health Sciences