Menopause and ovarian hormone-induced changes on forebrain cholinergic and GABAergic circuitry: Connecting the dots

Variations of surgical menopause have been shown to affect cognition in both rodents and humans. While the underlying mechanisms are unknown, data have indicated that the cholinergic and GABAergic systems play a role. This thesis aims to investigate how variations in surgical menopause modify neural forebrain circuitry, focusing on cholinergic and GABAergic neurons in brain regions vital to cognition, specifically the basal forebrain, the prefrontal cortex, and the hippocampus. Six-month-old rats received either Sham, ovariectomy (Ovx), or hysterectomy surgery. Six weeks after surgery, the rodents’ brains were collected, cryosectioned, immunostained, and imaged using confocal microscopy. Image analysis and cell density quantification were performed for cholinergic cells in the basal forebrain and GABAergic and NeuN+ cells in the medial prefrontal cortex and dorsal hippocampus. Overall, we found no significant changes in cell density between surgical groups. We did, however, observe enhanced activation of a small subset of cholinergic neurons in the medial septum of the basal forebrain in Ovx and Hysterectomy groups compared to Shams. In the medial prefrontal cortex, we found a strong trend toward increased activation of VIP neurons and presumptive excitatory neurons expressing NeuN in the Hysterectomy group compared to Shams. Collectively, results suggest that Ovx or hysterectomy surgery induces selective changes in neural circuitry and neuronal activity throughout the forebrain, which may underlie deficits associated with surgical menopause variations. While further research is needed to determine the mechanism behind these changes, these findings provide valuable insights into potential target areas for therapy and treatment.