Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Neurogenesis in the adult human hippocampus

Nature Medicine volume 4, pages 1313–1317 (1998)Cite this article

Abstract

The genesis of new cells, including neurons, in the adult human brain has not yet been demonstrated. This study was undertaken to investigate whether neurogenesis occurs in the adult human brain, in regions previously identified as neurogenic in adult rodents and monkeys. Human brain tissue was obtained postmortem from patients who had been treated with the thymidine analog, bromodeoxyuridine (BrdU), that labels DNA during the S phase. Using immunofluorescent labeling for BrdU and for one of the neuronal markers, NeuN, calbindin or neuron specific enolase (NSE), we demonstrate that new neurons, as defined by these markers, are generated from dividing progenitor cells in the dentate gyrus of adult humans. Our results further indicate that the human hippocampus retains its ability to generate neurons throughout life.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Newly generated cells can be detected in the adult human brain in patients previously treated with BrdU.
Figure 2: Quantitation of newly generated cells in the adult human hippocampus.
Figure 3: Newly generated cells in the adult human dentate gyrus can express a neuronal phenotype.
Figure 4: Newly generated cells in the adult human dentate gyrus can express additional neuronal phenotypes.
Figure 5: Brightfield double-immunohistochemical demonstration of neuronal phenotype.

Similar content being viewed by others

References

  1. Altman, J. &. Das, G.D. Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. >J. Comp. Neurol. 124, 319–335 ( 1965).

    Article  CAS  Google Scholar 

  2. Altman, J. & Das, G.D. Postnatal neurogenesis in the guinea-pig. Nature 214, 1098–1101 (1967).

    Article  CAS  Google Scholar 

  3. Caviness, V.S. Time of neuron origin in the hippocampus and dentate gyrus of normal and reeler mutant mice: an autoradiographic analysis. J. Comp. Neurol. 151, 113–120 (1973).

    Article  Google Scholar 

  4. Gueneau, G., Privat, A., Drouet, J. & Court, L. Subgranular zone of the dentate gyrus of young rabbits as a secondary matrix. A high-resolution autoradiographic study. Dev. Neurosci. 5, 345–358 (1982).

    Article  CAS  Google Scholar 

  5. Kuhn, H.G., Dickinson-Anson, H. & Gage, F.H. Neurogenesis in the dentate gyrus of the adult rat: Age-related decrease of neuronal progenitor proliferation. J. Neurosci. 16, 2027–2033 ( 1996).

    Article  CAS  Google Scholar 

  6. Gould, E., Tanapat, P., McEwen, B.S., Flugge, G. & Fuchs, E. Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress. Proc. Natl. Acad. Sci. USA 95, 3168– 3171 (1998).

    Article  CAS  Google Scholar 

  7. Kaplan, M.S. & Bell, D.H. Mitotic neuroblasts in the 9-day-old and 11-month-old rodent hippocampus. J. Neurosci. 4 , 1429–1441 (1984).

    Article  CAS  Google Scholar 

  8. Kaplan, M.S. & Hinds, J.W. Neurogenesis in the adult rat: electron microscopic analysis of light radioautographs. Science 197, 1092–1094 (1977).

    Article  CAS  Google Scholar 

  9. Stanfield, B.B. & Trice, J.E. Evidence that granule cells generated in the dentate gyrus of adult rats extend axonal projections. Exp. Brain Res. 72, 399– 406 (1988).

    CAS  PubMed  Google Scholar 

  10. Cameron, H.A., Woolley, C.S., McEwen, B.S. & Gould, E. Differentiation of newly born neurons and glia in the dentate gyrus of the adult rat. Neuroscience 56, 337– 344 (1993).

    Article  CAS  Google Scholar 

  11. Dolbeare, F. Bromodeoxyuridine: a diagnostic tool in biology and medicine, Part I: Historical perspectives, histochemical methods and cell kinetics. Histochem. J. 27, 339–369 ( 1995).

    Article  CAS  Google Scholar 

  12. Kempermann, G., Kuhn, H.G. & Gage, F.H. Genetic influence on neurogenesis in the dentate gyrus of adult mice. Proc. Natl. Acad. Sci. USA 94, 10409–10414 (1997).

    Article  CAS  Google Scholar 

  13. del Rio, J.A. & Soriano, E. Immunocytochemical detection of 5'-bromodeoxyuridine incorporation in the central nervous system of the mouse. Dev. Brain Res. 49, 311– 317 (1989).

    Article  CAS  Google Scholar 

  14. Gundersen, H.J. et al. The new stereological tools: disector, fractionator, nucleator and point sampled intercepts and their use in pathological research and diagnosis. APMIS 96, 857–881 (1988).

    Article  CAS  Google Scholar 

  15. West, M.J. Regionally specific loss of neurons in the aging human hippocampus. Neurobiol. Aging 14, 287–293 (1993).

    Article  CAS  Google Scholar 

  16. Coggeshall, R.E. & Lekan, H.A. Methods for determining numbers of cells and synapses: a case for more uniform standards of review. J. Comp. Neurol. 364, 6– 15 (1996).

    Article  CAS  Google Scholar 

  17. Kempermann, G., Kuhn, H.G. & Gage, F.H. More hippocampal neurons in adult mice living in an enriched environmen Nature 386, 493– 495 (1997).

    Article  CAS  Google Scholar 

  18. Mullen, R.J., Buck, C.R. & Smith, A.M. NeuN, a neuronal specific nuclear protein in vertebrates. Development 116, 201–211 (1992).

    CAS  PubMed  Google Scholar 

  19. Wolf, H.K. et al. NeuN: A useful neuronal marker for diagnostic histopathology. J. Histochem. Cytochem. 44, 1167– 1171 (1996).

    Article  CAS  Google Scholar 

  20. Sloviter, R.S. Calcium-binding protein (calbindin-D28k) and parvalbumin immunocytochemistry: localization in the rat hippocampus with specific reference to the selective vulnerability of hippocampal neurons to seizure activity. J. Comp. Neurol. 280, 183–196 ( 1989).

    Article  CAS  Google Scholar 

  21. Schmechel, D., Marango, P.J., Zis, A.P., Brightman, M. & Goodwin, F.K. Brain enolases as specific markers of neuronal and glial cells. Science 199, 313– 315 (1978).

    Article  CAS  Google Scholar 

  22. Kirschenbaum, B. et al. In vitro neuronal production and differentiation by precursor cells derived from the adult human forebrain. Cereb. Cortex 4, 576–589 ( 1994).

    Article  CAS  Google Scholar 

  23. Rakic, P. Limits of neurogenesis in primates. Science 227, 1054–1056 (1985).

    Article  CAS  Google Scholar 

  24. Eckenhoff M.F. & Rakic, P. Nature and fate of proliferative cells in the hippocampal dentate gyrus during the life span of the rhesus monkey. J. Neurosci. 8, 2729 –2747 (1988).

    Article  CAS  Google Scholar 

  25. Kempermann, G., Kuhn, H.G. & Gage, F.H. Experience-induced neurogenesis in the senescent dentate gyrus. J. Neurosci. 18, 3206– 3212 (1998).

    Article  CAS  Google Scholar 

  26. Gage, F.H. et al. Survival and differentiation of adult neuronal progenitor cells transplanted to the adult brain. Proc. Natl. Acad. Sci. USA 92, 11879–11883 ( 1995).

    Article  CAS  Google Scholar 

  27. Suhonen, J.O., Peterson, D.A., Ray, J. & Gage, F.H. Differentiation of adult hippocampus-derived progenitors into olfactory neurons in vivo. Nature 383, 624–627 ( 1996).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank G. Kempermann, T. Palmer, E. Brandon, M.-C. Senut, K. Sakurada, L. Chehabeddine and M. L. Gage for their comments, and H. van Praag for the contribution of rat tissue. In addition, we thank L. Kitabayashi for technical assistance. This study was supported by grants from the Swedish Medical Research Council (project no. K98-12X-12535-01A), Faculty of Medicine, University of Göteborg, the Gunvor and Josef Anérs Stiftelse, the John and Brit Wennerströms Stiftelse for Neurologisk Forskning, the Rune and Ulla Amlövs Stiftelse for Neurologisk and Reumatologisk Forskning, NHR-fonden, Stiftelsen Göteborgs MS förenings forsknings och byggnadsfond, Stiftelsen Handlanden Hjalmar Svenssons Forskningsfond, Göteborgs Läkaresällskap, Hjärnfonden, The Swedish Society of Medicine, Stiftelsen Lars Hiertas Minne, Stiftelsen Assar Gabrielssons Fond and the Edit Jacobssons Fond and from NIA and NINDS and the Alzheimer's Association (F.H.G.) and the American Federation for Aging Research (D.A.P.).

Author information

Authors and Affiliations

  1. Department of Clinical Neuroscience, Institute of Neurology Sahlgrenska University Hospital, Göteborg, 41345, Sweden

    Peter S. Eriksson, Ekaterina Perfilieva & Ann-Marie Alborn

  2. Department of Clinical Neuroscience, Department of Oncology, Sahlgrenska University Hospital, Göteborg, 41345, Sweden

    Thomas Björk-Eriksson

  3. Department of Clinical Neuroscience, Department of Pathology, Sahlgrenska University Hospital, Göteborg, 41345, Sweden

    Claes Nordborg

  4. Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, 92037, California, USA

    Peter S. Eriksson, Daniel A. Peterson & Fred H. Gage

Authors
  1. Peter S. Eriksson
    View author publications

    Search author on:PubMed Google Scholar

  2. Ekaterina Perfilieva
    View author publications

    Search author on:PubMed Google Scholar

  3. Thomas Björk-Eriksson
    View author publications

    Search author on:PubMed Google Scholar

  4. Ann-Marie Alborn
    View author publications

    Search author on:PubMed Google Scholar

  5. Claes Nordborg
    View author publications

    Search author on:PubMed Google Scholar

  6. Daniel A. Peterson
    View author publications

    Search author on:PubMed Google Scholar

  7. Fred H. Gage
    View author publications

    Search author on:PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Eriksson, P., Perfilieva, E., Björk-Eriksson, T. et al. Neurogenesis in the adult human hippocampus. Nat Med 4, 1313–1317 (1998). https://doi.org/10.1038/3305

Download citation

  • Received:

  • Accepted:

  • Issue date:

  • DOI: https://doi.org/10.1038/3305

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing