Glucoregulation and coping behavior after chronic stress: sex differences across the lifespan

Abstract

Exposure to prolonged stress during adolescence taxes adaptive and homeostatic processes leading to deleterious behavioral and metabolic outcomes. Although previous pre-clinical studies found effects of early life stress on cognition and stress hormone reactivity, these studies largely focused on males. The purpose of the current study was to determine how biological sex shapes behavioral coping and metabolic health across the lifespan after chronic stress. We hypothesized that examining chronic stress-induced behavioral and endocrine outcomes would reveal sex differences in the biological basis of susceptibility. During the late adolescent period, male and female Sprague-Dawley rats experienced chronic variable stress (CVS). Following completion of CVS, all rats experienced a forced swim test (FST) followed 3 days later by a fasted glucose tolerance test (GTT). The FST was used to determine coping in response to a stressor. Endocrine metabolic function was evaluated in the GTT by measuring glucose and corticosterone, the primary rodent glucocorticoid. Animals then aged to 15 months when the FST and GTT were repeated. In young animals, chronically stressed females exhibited more passive coping and corticosterone release in the FST. Additionally, chronically stressed females had elevated corticosterone and impaired glucose clearance in the GTT. Aging affected all measurements as behavioral and endocrine outcomes were sex specific. Furthermore, regression analysis between hormonal and behavioral responses identified associations depending on sex and stress. Collectively, these data indicate female susceptibility to the effects of chronic stress during adolescence. Further, translational investigation of coping style and glucose homeostasis may identify biomarkers for stress-related disorders.

Sex-Specific Cardiac Remodeling in Aged Rats after Early-Life Chronic Stress: Associations with Endocrine and Metabolic Factors

“…S1) did not have main effects or interactions that involved hypertrophy. Instead, the sex and stress effects previously reported for CVS to modify glucose mobilization and corticosterone secretion in a sex-specific manner [21] largely persisted after tertile separation.…”

“…The current data focus on inward left ventricular hypertrophy and associated factors. Our prior work reports group measures from the FST and GTT [21]. Therefore, while main effects are stated below, sex-and stressspecific differences are outlined in the supplemental material.…”

“…Tukey multiple comparisons post-tests were used when significant main or interaction effects were present. Area under the curve (AUC) analysis was calculated as previously reported [21]. Effect size is reported as eta squared (η 2 ).…”

“…Animals were weaned into same-sex group housing at PN24 and then pair-housed beginning PN35 through the remainder of the study. All estrous cycle phases were represented in female groups [21].…”

“…Additionally, our prior work found that adolescent chronic variable stress (CVS) increases glucocorticoid responses to the forced swim test (FST) in both male and female rats. However, only female rats have impaired glucose clearance after CVS, which manifests as altered glucoregulation in later life [21]. Yet, the long-term consequences of early-life chronic stress for sex-specific cardiovascular health and disease susceptibility are unknown.…”