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

Abstract

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 ages of F344 rats (2, 6, 9 and 14 months). The rats were ovariectomized (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. Coinciding with this pattern of neurogenic decline, we also detect adaptive changes in estrogen and progesterone receptor expression, antioxidant expression, and brain E2/P4 levels. 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.