Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults
Open accessAbstract
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.
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It is well accepted that neurogenesis sharply decreases in the aged mammalian nervous system, with no new neurons detectable in mice by 10 months of age.
“It is well accepted that neurogenesis sharply decreases in the aged mammalian nervous system29–31, with no new neurons detectable in mice by 10 months of age29,31.”
From Therapeutically viable generation of neurons with antisense oligonucleotide suppression of PTB (2021) · cites this paper as [30]
The paper’s Abstract reports a sharp early decline in hippocampal neurogenesis in humans and a decline during juvenile development in macaques. It does not report that no new neurons are detectable in mice by 10 months of age; that species-specific claim is unsupported by this source. (LLM, conf=0.88)
Experimental — accuracy not yet measuredSome groups report absent or minimal hippocampal neurogenesis in the mature brain using double immunofluorescence and single nucleus transcriptomics.
“Some groups have reported absent or minimal hippocampal neurogenesis in the mature brain using double immunofluorescence targeting markers expressed by neuronal cells at different maturational stages95, 96 and single nucleus transcriptomics97.”
From Dysregulation of adult hippocampal neuroplasticity in major depression: Pathogenesis and therapeutic implications (2022) · cites this paper as [95]
Adult hippocampal neurogenesis appears to occur in humans as well as in rodents, although this idea is still controversial.
“Adult hippocampal neurogenesis appears to occur in humans as well as in rodents, although this idea is still controversial (36, 37).”
From IL4-driven microglia modulate stress resilience through BDNF-dependent neurogenesis (2021) · cites this paper as [36]
The majority of reports provide positive evidence for adult neurogenesis in the human hippocampus, suggesting that studying this process in rodents is likely relevant to understanding human brain plasticity.
“A few studies contradict these findings (Cipriani et al., 2018; Sorrells et al., 2018), but the majority of reports provide positive evidence for adult neurogenesis in the hippocampus of humans, suggesting that studying this process in rodents is likely relevant to understanding human brain plasticity.”
From Adult neurogenesis, glia, and the extracellular matrix (2019) · cites this paper as Sorrells et al., 2018
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- Authors
- Sorrells, S. F., Paredes, M. F., Cebrian-Silla, A., Sandoval, K., Qi, D., Kelley, K. W., James, D., Mayer, S., Chang, J., Auguste, K. I., Chang, E. F., Gutierrez, A. J., Kriegstein, A. R., Mathern, G. W., Oldham, M. C., Huang, E. J., Garcia-Verdugo, J. M., Yang, Z., & Alvarez-Buylla, A.
- Affiliations
- University of California, San Francisco (US)
- Shanghai Medical College of Fudan University (CN)
- University of California, Los Angeles (US)
- Hospital Universitari i Politècnic La Fe (ES)
- Corresponding author
- Yang, Zhengang
- ORCID
- Venue
- Nature
- Published
- 2018-03
- Volume
- 555
- Issue
- 7696
- Pages
- 377-381
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6179355
- OpenAlex
- W2789329186
- Cited by
- 1,422
- References
- 34
- Citations by year
- 2026: 61 · 2025: 106 · 2024: 126 · 2023: 150 · 2022: 136 · 2021: 195 · 2020: 220 · 2019: 243 · 2018: 179 · 2017: 2 · 2012: 1
- FWCI
- 76.92
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Mental Health (F32MH103003, U01MH108898, R01MH113896)
- National Institute of General Medical Sciences (T32GM007618)
- National Institute of Neurological Disorders and Stroke (NS083823, K08NS091537, P01NS083513, R01NS028478, R01NS083823)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- adult neurogenesis, dentate gyrus, subgranular zone, neural progenitor cells, postnatal development, childhood, rhesus monkeys, epilepsy, postmortem brain, learning and memory
- MeSH terms
- Adolescent, Adult, Aged, Animals, Animals, Newborn, Cell Count, Child, Child, Preschool, Epilepsy, Female, Hippocampus, Humans, Infant, Macaca mulatta, Male, Middle Aged, Neurons, Dentate Gyrus, Fetal Development, Cell Proliferation, Neurogenesis, Young Adult, Neural Stem Cells, Healthy Volunteers
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