Table of Contents

Evidences for Adult Hippocampal Neurogenesis in Humans

  1. María Llorens-Martín1,2,3
  1. 1Department of Molecular Neuropathology, Centro de Biología Molecular “Severo Ochoa” (CBMSO), Spanish Research Council (CSIC)-Universidad Autónoma de Madrid (UAM), 28049 Madrid, Spain
  2. 2Department of Molecular Biology, Faculty of Sciences, Universidad Autónoma de Madrid, 28049 Madrid, Spain
  3. 3Center for Networked Biomedical Research on Neurodegenerative Diseases, 28031 Madrid, Spain
  4. 4Neuropathology Department, CIEN Foundation, 28031 Madrid, Spain
  1. Author contributions: M.L.-M. wrote the manuscript and obtained funding; E.P.M.-J., M.F.-G., J.T.-R., and M.L.-M. performed the experiments; A.R. performed autopsies and provided macroscopic images; E.M.J., J.T.-R., M.F.-G., A.R., and M.L.-M. revised, discussed, and approved the final version of the manuscript.

  2. ↵*E.P.M.-J, J.T.-R, and M.F.-G contributed equally to this work.

Abstract

The rodent hippocampus generates new neurons throughout life. This process, named adult hippocampal neurogenesis (AHN), is a striking form of neural plasticity that occurs in the brains of numerous mammalian species. Direct evidence of adult neurogenesis in humans has remained elusive, although the occurrence of this phenomenon in the human dentate gyrus has been demonstrated in seminal studies and recent research that have applied distinct approaches to birthdate newly generated neurons and to validate markers of adult-born neurons. Our data point to the persistence of AHN until the 10th decade of human life, as well as to marked impairments in this process in patients with Alzheimer's disease. Moreover, our work demonstrates that the methods used to process and analyze postmortem human brain samples can limit the detection of various markers of AHN to the point of making them undetectable. In this Dual Perspectives article, we highlight the critical methodological aspects that should be strictly controlled in human studies and the robust evidence that supports the occurrence of AHN in humans. We also put forward reasons that may account for current discrepancies on this topic. Finally, the unresolved questions and future challenges awaiting the field are highlighted.

  • Received March 25, 2020.
  • Revision received July 20, 2020.
  • Accepted September 28, 2020.

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