Neurogenesis: Mechanisms, Regulation, and Implications for Brain Function and Disease

Adult neurogenesis, the continuous generation of functional neurons from neural stem cells in the mature mammalian brain, represents one of the most remarkable forms of structural plasticity in the central nervous system. Once considered impossible, adult neurogenesis is now recognized as a fundamental process occurring primarily in two canonical neurogenic niches: the subgranular zone (SGZ) of the hippocampal dentate gyrus and the subventricular zone (SVZ) of the lateral ventricles. This review synthesizes current knowledge on adult neurogenesis, covering the cellular and molecular mechanisms underlying neural stem cell maintenance and neuronal differentiation, the stages of neurogenesis from proliferation to synaptic integration, the functional contributions of adult-born neurons to learning, memory, and mood regulation, and the modulation of neurogenesis by intrinsic and extrinsic factors. We examine the impact of aging and disease on neurogenesis, with particular emphasis on the ongoing debate regarding adult human neurogenesis. Recent conflicting reports about the extent and persistence of neurogenesis in the adult human brain have highlighted critical methodological challenges and species differences that must be addressed for successful clinical translation. We discuss evidence for and against human adult neurogenesis, the methodological factors contributing to discrepancies, and the implications for understanding human brain function and developing therapeutic strategies. This review also covers therapeutic strategies targeting neurogenic processes, including behavioral interventions, pharmacological approaches, and emerging cell-based therapies. Recent advances in molecular profiling, lineage tracing, and imaging technologies have deepened our understanding while revealing the complexity of neurogenic regulation across species and throughout the lifespan. This review aims to provide researchers, clinicians, and students with an integrative perspective on adult neurogenesis with special attention to translating findings from animal models to human applications.