Citation

Russell AL, Richardson MR, Bauman BM, Hernandez IM, Saperstein S, Handa RJ, Wu TJ. Endocrinology 2018; 159(6): 2363-2375.

Affiliation

Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda, MD.

Copyright

(Copyright © 2018, Endocrine Society)

DOI

10.1210/en.2018-00203

PMID

29701827

Abstract

Traumatic brain injury (TBI) affects 10 million people world-wide, annually. TBI is linked to increased risk of psychiatric disorders. TBI induced by explosive devices has a unique phenotype. Over 1/3 of people exposed to blast-induced (b)TBI have prolonged neuroendocrine deficits, shown by anterior pituitary dysfunction. Dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis is linked to increased risk for psychiatric disorders. Not only is there limited information on how the HPA axis responds to mild (m)bTBI, sex differences are understudied. We examined central and peripheral HPA axis reactivity 7-10 days after mbTBI in male and female mice. Males exposed to mbTBI had increased restraint-induced serum corticosterone (CORT), but attenuated restraint-induced corticotropin-releasing factor (CRF)/c-FOS-immunoreactivity (ir) in the paraventricular nucleus of the hypothalamus (PVN). Females displayed an opposite response, with attenuated restraint-induced CORT and enhanced restraint-induced PVN CRF/c-FOS-ir. We examined potential mechanisms underlying this dysregulation and found that mbTBI did not affect pituitary (POMC, CRFR1) or adrenal (11β-OHase, 11β-HSD1 and Mc2R) gene expression. mbTBI did not alter MR or GR gene expression in the PVN or relevant limbic structures. In females, but not males, mbTBI decreased c-FOS-ir in non-neuroendocrine (presumably pre-autonomic) CRF neurons in the PVN. While we demonstrated a sex-dependent link to stress dysregulation of pre-autonomic neurons in females, we hypothesize that mbTBI may disrupt limbic pathways involved in HPA axis coordination in males. Overall, mbTBI altered the HPA axis in a sex-dependent manner, highlighting the importance of developing therapies to target individual strategies that males and females utilize to cope with mbTBI.

Language: en