Journal
NATURE
Volume 555, Issue 7696, Pages 377-+Publisher
NATURE RESEARCH
DOI: 10.1038/nature25975
Keywords
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Categories
Funding
- NIH [P01 NS083513, R01 NS028478]
- NIH NINDS [NS083823, U01 MH108898]
- UCSF Weill Institute for Neurosciences
- NSFC [31425011, 31630032, 31421091]
- European Molecular Biology Organization (EMBO Long-Term Fellowship) [ALTF_393-2015]
- German Research Foundation (DFG) [MA 7374/1-1]
- MINECO/FEDER [BFU2015-64207-P]
- Red de Terapia Celular TerCel
- Instituto de Salud Carlos III [ISCIII2012-RED-19-016, RD12/0019/0028]
- [F32 MH103003]
- [K08 NS091537]
- [PROMETEOII/2014/075]
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New neurons continue to be generated in the subgranular zone of the dentate gyrus of the adult mammalian hippocampus(1-5). This process has been linked to learning and memory, stress and exercise, and is thought to be altered in neurological disease(6-10). In humans, some studies have suggested that hundreds of new neurons are added to the adult dentate gyrus every day(11), whereas other studies find many fewer putative new neurons(12-14). Despite these discrepancies, it is generally believed that the adult human hippocampus continues to generate new neurons. Here we show that a defined population of progenitor cells does not coalesce in the subgranular zone during human fetal or postnatal development. We also find that the number of proliferating progenitors and young neurons in the dentate gyrus declines sharply during the first year of life and only a few isolated young neurons are observed by 7 and 13 years of age. In adult patients with epilepsy and healthy adults (18-77 years; n = 17 post-mortem samples from controls; n = 12 surgical resection samples from patients with epilepsy), young neurons were not detected in the dentate gyrus. In the monkey (Macaca mulatta) hippocampus, proliferation of neurons in the subgranular zone was found in early postnatal life, but this diminished during juvenile development as neurogenesis decreased. We conclude that recruitment of young neurons to the primate hippocampus decreases rapidly during the first years of life, and that neurogenesis in the dentate gyrus does not continue, or is extremely rare, in adult humans. The early decline in hippocampal neurogenesis raises questions about how the function of the dentate gyrus differs between humans and other species in which adult hippocampal neurogenesis is preserved.
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