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Nature. 2018 Mar 15;555(7696):377-381. doi: 10.1038/nature25975. Epub 2018 Mar 7.

Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults.

Author information

1
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, California 94143, USA.
2
Department of Neurological Surgery, University of California San Francisco, San Francisco, California 94143, USA.
3
Department of Neurology, University of California San Francisco, San Francisco, California 94143, USA.
4
Laboratorio de Neurobiología Comparada, Instituto Cavanilles, Universidad de Valencia, CIBERNED, Valencia, 46980, Spain.
5
State Key Laboratory of Medical Neurobiology and Institutes of Brain Science, Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
6
David Geffen School of Medicine, Department of Neurosurgery, Intellectual Development and Disabilities Research Center, University of California Los Angeles, Los Angeles, California 90095, USA.
7
Unidad de Cirugía de la Epilepsia, Hospital Universitario La Fe, Valencia 46026, Spain.
8
Department of Neurosurgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, USA.
9
Department of Psychiatry and Biobehavioral Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, USA.
10
Department of Pathology, University of California San Francisco, San Francisco, California 94143, USA.

Abstract

New neurons continue to be generated in the subgranular zone of the dentate gyrus of the adult mammalian hippocampus. This process has been linked to learning and memory, stress and exercise, and is thought to be altered in neurological disease. In humans, some studies have suggested that hundreds of new neurons are added to the adult dentate gyrus every day, whereas other studies find many fewer putative new neurons. 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.

PMID:
29513649
PMCID:
PMC6179355
DOI:
10.1038/nature25975
[Indexed for MEDLINE]
Free PMC Article

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