Exploring the Role of PGC-1α in Adult Neurogenesis and its Impact on Behavior

Abstract

Adult hippocampal neurogenesis, the process of generating new neurons throughout life, remains a dynamic and tightly regulated process, vital for cognitive performance and emotional regulation. Being an energetically demanding process, its regulation by mitochondria remains incompletely understood. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) is a master regulator of mitochondrial function, yet its role in adult neurogenesis has not been clearly defined. Here, we investigate the necessity of PGC-1α in neural stem and progenitor cells (NSPCs) in a tamoxifen-inducible conditional knockout (cKO) mouse model. Using immunohistochemistry and behavioral assays, we assessed the consequences of PGC-1α loss on neurogenesis, anxiety and cognition at 3- and 6-months post-tamoxifen administration. Quantification of neurogenesis markers revealed a significant impairment by 3 months post-induction. Behaviorally, PGC-1α cKO mice displayed a temporary improvement in anxiety and working memory, neither of which were sustained, while spatial learning and memory results were inconclusive. Interestingly however, a significant long-term recognition memory deficit emerged in male cKO mice at 6 months post-induction. Our findings suggest that PGC-1α is essential for maintaining adult hippocampal neurogenesis and long-term recognition memory.