Prepubertal ovariectomy confers resilience to stress-induced anxiety in adult female mice.

The increased vulnerability to stress-induced neuropsychiatric disorders in women, including anxiety disorders, does not emerge until pubertal onset, suggesting a role for ovarian hormones in organizing sex-specific vulnerability to anxiety. Parvalbumin (PV) interneurons in the prefrontal cortex are a potential target for these ovarian hormones. PV+ interneurons undergo maturation during the adolescent period and have been shown to be sensitive to stress and to mediate stress-induced anxiety in female mice. To test the idea that ovarian hormones at puberty are necessary for the acquisition of sensitivity to stress, hypothetically driving the response of PV+ interneurons to stress, we performed ovariectomy or sham surgery before pubertal onset in female mice. These mice then were exposed to four weeks of unpredictable chronic mild stress in adulthood. We then assessed anxiety-like behavior and PV/FosB colocalization in the medial PFC. Additionally, we assessed stress-induced anxiety-like behavior in female mice following ovariectomy in adulthood to determine if puberty is a sensitive period for ovarian hormones in mediating vulnerability to stress. We found that prepubertal ovariectomy protects against the development of anxiety-like behavior in adulthood, an effect not found following ovariectomy in adulthood. This effect may be independent of ovarian hormones on prefrontal PV+ interneurons response to stress.