Dynamics of hippocampal neurogenesis in adult humans
Open accessAbstract
Adult-born hippocampal neurons are important for cognitive plasticity in rodents. There is evidence for hippocampal neurogenesis in adult humans, although whether its extent is sufficient to have functional significance has been questioned. We have assessed the generation of hippocampal cells in humans by measuring the concentration of nuclear-bomb-test-derived ¹⁴C in genomic DNA, and we present an integrated model of the cell turnover dynamics. We found that a large subpopulation of hippocampal neurons constituting one-third of the neurons is subject to exchange. In adult humans, 700 new neurons are added in each hippocampus per day, corresponding to an annual turnover of 1.75% of the neurons within the renewing fraction, with a modest decline during aging. We conclude that neurons are generated throughout adulthood and that the rates are comparable in middle-aged humans and mice, suggesting that adult hippocampal neurogenesis may contribute to human brain function.
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About 35% of the whole population of the dentate gyrus in humans undergoes replacement, while in the mouse this fraction is limited to only 10%.
“Interestingly, about 35% of the whole population of the dentate gyrus in humans undergoes replacement (Spalding et al., 2013), while in the mouse this fraction is limited to only 10% (Imayoshi et al., 2008).”
From Depression and adult neurogenesis: Positive effects of the antidepressant fluoxetine and of physical exercise (2018) · cites this paper as Spalding et al., 2013
The Results section, “A large proportion of hippocampal neurons is subject to turnover,” estimates that 35% (CI 12%–63%) of human hippocampal neurons are in the cycling population. It says this corresponds to the vast majority of dentate gyrus neurons, not 35% of dentate gyrus neurons. The mouse figure is separately attributed to Imayoshi et al. in the citing sentence and is not part of this verdict. (LLM, conf=0.92)
Experimental — accuracy not yet measuredNeurogenesis in humans displays a higher turnover than in rodents.
“neurogenesis in human displays a higher turnover than in rodents (Spalding et al., 2013;Imayoshi et al., 2008)”
From Depression and adult neurogenesis: Positive effects of the antidepressant fluoxetine and of physical exercise (2018) · cites this paper as Spalding et al., 2013
The Discussion reports that a much larger proportion of hippocampal neurons undergoes exchange in humans than in mice. That supports a higher proportion turning over, but not a higher turnover rate: the Abstract says rates are comparable in middle-aged humans and mice. The claim does not distinguish between those meanings of turnover. (LLM, conf=0.84)
Experimental — accuracy not yet measuredIn humans, a post mortem study measuring 14C in genomic DNA reported a daily number of 700 new neurons with a modest decline during aging.
“Yet, in humans a post mortem study measuring the concentration of nuclear bomb test-derived 14 C in genomic DNA reported a daily number of 700 new neurons with a modest decline during aging (Spalding et al., 2013).”
From Serotonin and neuroplasticity – Links between molecular, functional and structural pathophysiology in depression (2017) · cites this paper as Spalding et al., 2013
In the human dentate gyrus, neurogenesis takes place at a rate of about 700 neurons generated per day and the production of new neurons decreases steadily with age.
“After a first evidence indicating that adult neurogenesis occurs also in humans in the dentate gyrus (Eriksson et al., 1998), more recent data show that in the human dentate gyrus neurogenesis takes place at a rate of about 700 neurons generated per day and that the production of new neurons decreases steadily with age (Spalding et al., 2013;Knoth et al., 2010;Mathews et al., 2017).”
From Depression and adult neurogenesis: Positive effects of the antidepressant fluoxetine and of physical exercise (2018) · cites this paper as Spalding et al., 2013
In adult humans, new neurons continue to be generated with a modest decline during aging.
“Most of the post-mortem studies have now evidenced that in adult humans, new neurons continued to be generated with a modest decline during aging (Eriksson et al. 1998; Reif et al. 2006; Spalding et al. 2013).”
From Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression (2018) · cites this paper as Spalding et al. 2013
Exercise has numerous neuroprotective and cognitive benefits, especially for memory and learning.
“It has now been established that exercise, even among minimal commitment exercise routines, has an array of robust effects on the brain, such as enhanced memory, mood, cognitive functioning, plasticity, and learning capabilities (Erickson et al., 2011; Spalding et al., 2013; Phillips et al., 2014).”
From Exercise-Mediated Neurogenesis in the Hippocampus via BDNF (2018) · cites this paper as Spalding et al., 2013
The Discussion links adult-born hippocampal neurons to synaptic plasticity and memory-related pattern separation, but does not link those effects to exercise. A search of our copy for exercise and related benefits found no passage addressing whether exercise improves memory, mood, cognition, plasticity, or learning, including with minimal exercise routines. (LLM, conf=0.76)
Experimental — accuracy not yet measuredThe ability to visualize newborn neurons depends heavily on tissue fixation procedures, experimental protocols, and subject selection.
“The ability to visualize newborn neurons is heavily dependent on tissue fixation procedures, experimental protocols, and subject selection, as previously described102, 104, 105.”
From Dysregulation of adult hippocampal neuroplasticity in major depression: Pathogenesis and therapeutic implications (2022) · cites this paper as [102]
The authors' group and others have shown evidence of neurogenesis throughout adulthood using double immunofluorescence, in situ hybridization, and 14C decay-defined neuronal age.
“However, our group and others have shown evidence of neurogenesis throughout adulthood using double immunofluorescence98-101, in situ hybridization102 and 14C decay-defined neuronal age103.”
From Dysregulation of adult hippocampal neuroplasticity in major depression: Pathogenesis and therapeutic implications (2022) · cites this paper as [102]
FANS has been used to bypass the incompatibility of neurons with whole-cell sorting.
“A novel variant of FACS, fluorescence activated nuclei sorting (FANS), has recently been used to bypass the incompatibility of neurons with whole-cell sorting.”
From Decoding neuroproteomics: integrating the genome, translatome and functional anatomy (2014) · cites this paper as [113]
Purification of striatal nuclei by NEUN labelling led to observations of adult human neurogenesis in the hippocampus.
“purification of striatal nuclei by NEUN labelling has led to interesting observations of adult human neurogenesis in the hippocampus113”
From Decoding neuroproteomics: integrating the genome, translatome and functional anatomy (2014) · cites this paper as [113]
The subgranular zone of the hippocampal dentate gyrus is one of just two primary locations where neurogenesis is known to occur in the adult rodent and human brain.
“The subgranular zone of the hippocampal dentate gyrus (DG) is one of the just two primary locations where neurogenesis is known to occur in the adult rodent and human brain (Spalding et al., 2013; Kempermann et al., 2015).”
From Aerobic Exercise as a Tool to Improve Hippocampal Plasticity and Function in Humans: Practical Implications for Mental Health Treatment (2016) · cites this paper as Spalding et al., 2013
Spalding et al showed increased 14C levels in human hippocampal genomic DNA, indicative of postnatal neurogenesis, into at least the fifth decade of life.
“In an elegant study based on the idea that replicating DNA in human neurons incorporate atmospheric 14 C radioactive carbon, Spalding et al (2013) showed increased 14 C levels in human hippocampal genomic DNA, indicative of postnatal neurogenesis, into at least the fifth decade of life (Spalding et al, 2013).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Spalding et al, 2013
New neurons were generated at a rate of 1.75% during adulthood with a modest but significant decline with old age.
“New neurons were generated at a rate of 1.75% during adulthood with a modest but significant decline with old age.”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Spalding et al, 2013
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- Authors
- Spalding, K. L., Bergmann, O., Alkass, K., Bernard, S., Salehpour, M., Huttner, H. B., Boström, E., Westerlund, I., Vial, C., Buchholz, B. A., Possnert, G., Mash, D. C., Druid, H., & Frisén, J.
- Affiliations
- Karolinska Institutet (SE)
- Lyon 1 Université (FR)
- Uppsala University (SE)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Centre National de la Recherche Scientifique (FR)
- Lawrence Livermore National Laboratory (US)
- University of Miami (US)
- Corresponding author
- Frisén, Jonas
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2013-06
- Volume
- 153
- Issue
- 6
- Pages
- 1219-1227
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4394608
- OpenAlex
- W2136863044
- Cited by
- 1,841
- References
- 51
- Citations by year
- 2026: 54 · 2025: 92 · 2024: 94 · 2023: 99 · 2022: 131 · 2021: 157 · 2020: 169 · 2019: 166 · 2018: 190 · 2017: 180 · 2016: 166 · 2015: 161 · 2014: 135 · 2013: 45
- FWCI
- 62.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
- HAL (submittedVersion)
- Funders
- Foundation for the National Institutes of Health
- U.S. Department of Energy
- National Alliance for Research on Schizophrenia and Depression
- Deutsche Forschungsgemeinschaft
- Karolinska Institutet
- Knut och Alice Wallenbergs Stiftelse
- Stockholms Läns Landsting
- Vetenskapsrådet
- Rättsmedicinalverket
- National Institute on Drug Abuse (R01DA031429, DA031429)
- National Institute of General Medical Sciences (P41GM103483)
- National Center for Research Resources (P41RR013461)
- 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 hippocampal neurogenesis, hippocampal neurons, cell turnover, cognitive plasticity, aging
- MeSH terms
- Adult, Aging, Animals, Hippocampus, Humans, Models, Biological, Neurons, Mice, Radiometric Dating, Neurogenesis
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