The effects of prepubertal ovariectomy and chronic stress on activity of brain limbic regions in adult mice.

Abstract

Women are twice as likely than men to develop an anxiety disorder after stress exposure stress, a sex-specific vulnerability that arises after puberty. This suggests that pubertal hormones could contribute to the central changes induced by stress and leading to behavioral deregulations. The main brain regions involved in stress-induced psychopathologies are part of the limbic system, including the prefrontal cortex (PFC), the basolateral amygdala (BLA) and the ventral hippocampus (vHipp). Changes in their activity are often reported after stress, contributing to appearance of behavioral symptoms. We aimed at determining whether female pubertal hormones modulate the effects of chronic stress on activity of these limbic regions to identify a potential mechanism underlying the female vulnerability to stress-induced pathologies. Prepubertal adolescent female mice underwent ovariectomy (OVX) or sham surgery. In late adolescence, they started 4 weeks of unpredictable chronic mild stress (UCMS). We used immunohistochemistry to quantify FosB/ΔFosB, a marker of chronic activity, in the PFC, BLA, and vHipp. Prepubertal OVX increased activity of the PFC and decreased activity of the BLA and vHipp, while UCMS had little impact. The PFC was more significantly impacted by both OVX and UCMS, with each of these manipulations increasing number of FosB/ΔFosB+ cells, however without interactive effects. Correlation analyses indicate that level of activity in the PFC and vHipp correlates with measures of anxiety. However, the gonadal status influences strongly these relationships. Our data indicate that pubertal hormones could play a role in the regulation of anxiety through their long-lasting impact on the limbic system.