Investigating the Effects of Ovariectomy on Female Parvalbumin Interneuron Maturation Within the Ventral Hippocampus
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Date
2023-05
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The Ohio State University
Abstract
Female vulnerability to stress-induced neuropsychiatric disorders, including anxiety, does not emerge until pubertal onset. This suggests that an increase in circulating ovarian hormones at puberty may have an organizational role during adolescence on developing brain circuitry associated with stress response. The ventral hippocampus (vHPC) is associated with emotional processing, and hyperactivity of the vHPC correlates with anxiety disorders. Activity within the vHPC has been shown to increase after chronic stress exposure, with this increase in activity being associated with decreased activity of inhibitory interneurons. Parvalbumin interneurons (PVIs) are a class of inhibitory interneurons regulating circuit activity throughout the brain and have been implicated in psychiatric conditions including anxiety. They undergo maturation during the adolescent period and have been shown to be highly sensitive to stress in adulthood, suggesting that sensitivity to stress is acquired during these maturational processes. Furthermore, PVIs maturation was found to be a process driven by estradiol in some regions; however, it is less clear if this is the case in the vHPC, and if this maturation renders vHPC PVI sensitive to stress in adulthood. Here, we proposed an investigation into the role of pubertal hormones on maturation of PVI in the vHPC, and the role of this maturation on stress-induced anxiety. We hypothesized that ovarian hormones during the pubertal period promote maturation of PVIs within the vHPC resulting in female vulnerability to anxiety disorders. We performed ovariectomy or sham surgery in female mice prior to pubertal onset. These mice underwent 4 weeks of unpredictable chronic mild stress (UCMS) in adulthood. We assessed anxiety-like behavior and PVI maturation in the vHPC. Additionally, we assessed anxiety-like behavior in female mice following ovariectomy in adulthood to determine if puberty is a sensitive period for the actions of estrogen on PVI maturation following UCMS. We found that prepubertal ovariectomy protects against the development of anxiety-like behavior following 4 weeks of UCMS in adulthood, an effect not found in ovariectomized adults. However, we found no effect of surgery on the ratio of PVIs/PNNs within the vHPC, highlighting a need for additional investigation into the molecular causes of female vulnerability to anxiety.
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Keywords
ventral hippocampus, anxiety, puberty, parvalbumin, perineuronal nets