Adult hippocampal neurogenesis

Adult hippocampal neurogenesis (AHN) is the process by which new neurons arise from neural stem and progenitor cells in the subgranular zone of the hippocampal dentate gyrus (DG) and integrate into granule-cell circuits involved in pattern separation, episodic memory encoding, and mood regulation. In rodents, newly born DG granule cells mature over roughly four to eight weeks, regulated by Wnt, Notch, and BDNF, before becoming synaptically incorporated. Whether AHN persists in adult humans remains one of the most actively debated questions in neuroscience. Two widely cited 2018 post-mortem studies reached opposite conclusions: Sorrells et al. (Nature 2018) found immature-neuron markers (DCX, PSA-NCAM) undetectable in human DG beyond early childhood, whereas Boldrini et al. (Cell Stem Cell 2018), using optimised tissue fixation, reported thousands of DCX-positive neuroblasts in donors up to 79 years old. Post-mortem interval, fixation duration, and antibody sensitivity are the leading explanation for the discrepancy. Radiocarbon birth-dating independently estimated approximately 1.75% annual turnover of DG neurons in adult humans (Spalding et al., Cell 2013). Aerobic exercise reliably elevates hippocampal BDNF and increases DG neurogenesis in rodents; whether the same causal link holds in adult humans is plausible but not yet demonstrated causally, making exercise-promoted AHN an inferential mechanism for associations between physical activity, hippocampal volume preservation, and delayed cognitive decline.