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.

  • Original Research Article
  • Published:

Depression: reduced number of granule cells in the hippocampus of female, but not male, rats due to prenatal restraint stress

Molecular Psychiatry volume 7, pages 810–813 (2002)Cite this article

Abstract

It has been hypothesized that decreased neurogenesis in the dentate gyrus may be involved in mediating depressive disorders, which are 1.5–3 times more frequent in women than in men. Additionally, prenatal stress may increase the risk of developing depression in adulthood. However, the interrelations between prenatal stress and the development of depression in adulthood, preferentially in females, are not understood. Here, we subjected pregnant rats to a single 20-min period of restraint stress on day 18 after mating. When the offspring were 75 days of age, the numbers of granule cells and pyramidal cells (area CA1–3) in the hippocampus were analyzed with the optical fractionator. The Cavalieri's principle was applied to analyze the volumes of both granule cell layer and pyramidal cell layer in the hippocampus. Prenatally stressed females, but not males, had reduced numbers of hippocampal granule cells compared to their non-prenatally stressed counterparts. This is the first report of a sex-specific difference concerning the reduction of the number of hippocampal granule cells due to prenatal stress. In humans, prenatal stress may induce cell loss in the granule cells of the hippocampus preferentially in females compared to males, and this may be a sex-specific predisposing factor for the development of depression in adulthood.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1

Similar content being viewed by others

References

  1. Frye CA, Walf AA . Changes in progesterone metabolites in the hippocampus can modulate open field and forced swim test behavior of proestrous rats Horm Behav (in press)

  2. Jacobs BL, Praag H, Gage FH . Adult brain neurogenesis and psychiatry: a novel theory of depression Mol Psychiatry 2000; 5: 262–269

    Article  CAS  Google Scholar 

  3. Sapolsky RM . Depression, antidepressants, and the shrinking hippocampus Proc Natl Acad Sci USA 2001; 98: 12320–12322

    Article  CAS  Google Scholar 

  4. Manji HK, Drevets WC, Charney DS . The cellular neurobiology of depression Nat Med 2001; 7: 541–547

    Article  CAS  Google Scholar 

  5. Watson JB, Mednick SA, Huttunen M, Wang X . Prenatal teratogens and the development of adult mental illness Dev Psychopathol 1999; 11: 457–466

    Article  CAS  Google Scholar 

  6. Dugovic C, Maccari S, Weibel L, Turek FW, Van Reeth O . High corticosterone levels in prenatally stressed rats predict persistent paradoxical sleep alterations J Neurosci 1999; 19: 8656–8664

    Article  CAS  Google Scholar 

  7. Ustun TB . Cross-national epidemiology of depression and gender J Gend Specif Med 2000; 3: 54–58

    CAS  PubMed  Google Scholar 

  8. Frye CA, Bayon LE . Prenatal stress reduces the effectiveness of the neurosteroid 3 alpha, 5 alpha-THP to block kainic-acid-induced seizures Dev Psychobiol 1999; 34: 227–234

    Article  CAS  Google Scholar 

  9. Schmitz C, Bultmann E, Gube M, Korr H . Neuron loss in the mouse hippocampus following prenatal injection of tritiated thymidine or saline Int J Dev Neurosci 1999; 17: 185–190

    Article  CAS  Google Scholar 

  10. Gould E, Gross CG . Neurogenesis in adult mammal: some progress and problems J Neurosci 2002; 22: 619–623

    Article  CAS  Google Scholar 

  11. Weinstock M . Alterations induced by gestational stress in brain morphology and behaviour of the offspring Prog Neurobiol 2001; 65: 427–451

    Article  CAS  Google Scholar 

  12. Rapp P, Gallagher M . Preserved neuron number in the hippocampus of aged rats with spatial learning deficits Proc Natl Acad Sci USA 1996; 93: 9926–9930

    Article  CAS  Google Scholar 

  13. Lemaire V, Koehl M, Le Moal M, Abrous DN . Prenatal stress produces learning deficits associated with an inhibition of neurogenesis in the hippocampus Proc Natl Acad Sci USA 2000; 97: 11032–11037

    Article  CAS  Google Scholar 

  14. Gould E, Cameron HA, Daniels DC, Woolley CS, McEwen BS . Adrenal hormones suppress cell division in the adult rat dentate gyrus J Neurosci 1992; 12: 3642–3650

    Article  CAS  Google Scholar 

  15. Czeh B, Michaelis T, Watanabe T, Frahm J, de Biurrun G, van Kampen M et al. Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine Proc Natl Acad Sci USA 2001; 98: 12796–12801

    Article  CAS  Google Scholar 

  16. Schmitz C, Hof PR . Recommendations for straightforward and rigorous methods of counting neurons based on a computer simulation approach J Chem Neuroanat 2000; 20: 93–114

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank H Helten for technical assistance, and BPF Rutten for help in generating Figure 1. This work was in part supported by a grant of the START program of the Faculty of Medicine of the RWTH University of Aachen (to CS), and by the US National Science Foundation (IBN98-96263 and DBI-0097343, to CA Frye).

Author information

Authors and Affiliations

  1. Department of Anatomy and Cell Biology, RWTH University of Aachen, Aachen, D-52057, Germany

    C Schmitz, M Bludau, P Ong, I Ueffing, J Vehoff & H Korr

  2. Department of Psychology, SUNY at Albany, Albany, NY, USA

    M E Rhodes & C A Frye

  3. Department of Histology and Embryology, Ondokuz Mayis University, Samsun, Turkey

    S Kaplan

  4. Department of Biological Sciences, SUNY at Albany, Albany, NY, USA

    C A Frye

  5. The Center for Neuroscience Research, SUNY at Albany, Albany, NY, USA

    C A Frye

Authors
  1. C Schmitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M E Rhodes
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M Bludau
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S Kaplan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. P Ong
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. I Ueffing
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J Vehoff
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. H Korr
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. C A Frye
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C Schmitz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schmitz, C., Rhodes, M., Bludau, M. et al. Depression: reduced number of granule cells in the hippocampus of female, but not male, rats due to prenatal restraint stress. Mol Psychiatry 7, 810–813 (2002). https://doi.org/10.1038/sj.mp.4001118

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.mp.4001118

Keywords

This article is cited by

Search

Advanced search

Quick links