Acute E2/P4 loss compromises the biology and function of neurogenic niches during a vulnerable female aging period

Effects of aging on neural stem progenitor cells (NSPCs) have been studied in males, but less is known in females. Here, we comparatively assess female NSPC biology, both in the subventricular zone and hippocampal dentate gyrus niches, across different age groups of F344 rats. The rats underwent ovariectomy (OVX) or remained Intact at each of the aging stages, to assess the role of the female sex hormones, estradiol (E2) and progesterone (P4). Results show that while age-dependent decays become prominent at 14 months, ovariectomy-induced E2/P4 loss markedly reduces neurogenesis and associated behavioral function, earlier, at 9 months of age. Alongside this, we also detected adaptive changes in estrogen and P4 receptor expression and antioxidant expression. E2/P4 treatment rescued the OVX-induced compromise in neurogenesis and behavior at 9 months. Fundamentally, these results reveal specific female time periods, when the brain is sensitive to age and E2/P4 loss, potentially "setting up" for disease susceptibility.