Chronic variable stress alters hypothalamic-pituitary-adrenal axis function in the female mouse

Area of Science:

• Neuroendocrinology
• Stress Physiology
• Behavioral Neuroscience

Background:

• The hypothalamic-pituitary-adrenal (HPA) axis regulates stress response but its dysregulation is linked to stress-related diseases.
• Sex differences exist in stress-related disorders, yet female subjects are underrepresented in preclinical research.
• Chronic stress impacts HPA axis function, potentially contributing to neuropsychiatric disorders.

Purpose of the Study:

• To investigate the effects of chronic variable stress (CVS) on HPA axis activity in female mice.
• To examine basal and stress-induced HPA axis responses following chronic stress exposure.
• To assess the impact of CVS on neuropeptide gene expression and behavior in females.

Main Methods:

• Utilized a chronic variable stress (CVS) paradigm in female C57BL/6 mice.
• Measured corticosterone (CORT) levels, adrenal hypertrophy, and PVN neuropeptide mRNA expression (CRH, AVP, OT).
• Assessed behavioral responses using light/dark box and tail suspension tests.

Main Results:

• CVS induced adrenal hypertrophy and altered evening HPA axis activity, including elevated basal CORT and blunted stress responses.
• CVS modified paraventricular nucleus (PVN) oxytocin (OT) and arginine vasopressin (AVP) mRNA responses to acute stress.
• Despite HPA axis changes, CVS did not affect anxiety- or depressive-like behaviors in female mice.

Conclusions:

• Chronic variable stress effectively models HPA axis dysregulation in female mice.
• CVS alters basal and stress-induced HPA axis activity, particularly in the evening.
• The findings suggest relevance for understanding stress-related diseases with sex-specific vulnerabilities.