Do new neurons grow in the adult human hippocampus? A review of the evidence

Abstract

Adult human hippocampal neurogenesis has been debated for decades, with methodological differences producing conflicting reports. Radiocarbon birth-dating provided population-level evidence of sustained dentate gyrus neuron turnover, while immunohistochemical studies produced variable results depending on fixation protocols. Optimized post-mortem handling has reported higher detectability of immature-neuron markers across adulthood, whereas longer post-mortem delays and prolonged fixation can reduce signal and contribute to apparent null findings; however, marker-based interpretations remain debated and require cautious, multi-marker validation. Recent single-nucleus and spatial transcriptomics further support persistent neurogenesis, identifying immature granule-cell signatures and niche programs into late life. This article critically appraises evidence from radiocarbon dating, immunohistochemistry, and transcriptomics, highlighting sources of discrepancy and convergence. Practical standards for human tissue handling, antigen retrieval, and multimarker panels are proposed to minimize methodological artefacts. Collectively, convergent evidence favors low-level, lifelong neurogenesis with potential contributions to memory precision and affective regulation, albeit at lower rates than rodents. It is concluded that integrating radiocarbon baselining, optimized immunohistochemistry, and transcriptomic validation provides a robust framework for resolving the controversy and advancing translational relevance in cognition, aging, and psychiatry.

Keywords

neurogenesis / carbon radioisotopes / doublecortin protein / transcriptome / tissue fixation

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