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Maternal separation alters nerve growth factor and corticosterone levels but not the DNA methylation status of the exon 17 glucocorticoid receptor promoter region

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Abstract

Separating rat pups from their mothers during the early stages of life is an animal model commonly used to study the development of psychiatric disorders such as anxiety and depression. The present study investigated how soon after the termination of the maternal separation period behavioural and neuroendocrine abnormalities relevant to above-mentioned illnesses would manifest. Sprague Dawley rat pups were subjected to maternal separation (3 h per day from postnatal day 2 through 14) and their behaviour and HPA axis activity determined 7 d later. We also measured nerve growth factor levels in their hippocampi and assessed the DNA methylation status of the promoter region of exon 17 of the glucocorticoid receptor in this brain region. As early as 7 d after the termination of the adverse event, a change in behaviour was observed that was associated with increased plasma corticosterone release and elevated nerve growth factor levels in the hippocampus. No alteration in the methylation status of the exon 17 glucocorticoid receptor promoter region was observed. Our data indicate that early life adversity may lead to the rapid development of abnormal behaviours and HPA axis dysregulation though no epigenetic changes to the exon 17 glucocorticoid receptor promoter region occurred. We further propose that the observed increased neurotrophin levels reflect compensatory mechanisms that attempt to combat the long-term deleterious effects of maternal separation.

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Acknowledgements

This study was financially supported by grants from the National Institutes of Health (NIH) Fogarty International Center (R01TW008040), the Medical Research Council of South Africa, and the National Research Foundation of South Africa. The authors wish to thank Ms Susan Giegel for editorial services rendered.

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Authors and Affiliations

  1. Discipline of Human Physiology, Faculty of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban, 4000, South Africa

    W. M. U. Daniels

  2. Division Medical Physiology, University of Stellenbosch, Tygerberg, South Africa

    L. R. Fairbairn & G. van Tilburg

  3. Division of Molecular Biology and Human Genetics, University of Stellenbosch, Tygerberg, South Africa

    C. R. E. McEvoy

  4. Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA

    M. J. Zigmond

  5. Department of Human Biology, University of Cape Town, Cape Town, South Africa

    V. A. Russell

  6. Department of Psychiatry, University of Cape Town, Cape Town, South Africa

    D. J. Stein

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  1. W. M. U. Daniels
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  2. L. R. Fairbairn
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  3. G. van Tilburg
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  4. C. R. E. McEvoy
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  5. M. J. Zigmond
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  6. V. A. Russell
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  7. D. J. Stein
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Correspondence to W. M. U. Daniels.

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Daniels, W.M.U., Fairbairn, L.R., van Tilburg, G. et al. Maternal separation alters nerve growth factor and corticosterone levels but not the DNA methylation status of the exon 17 glucocorticoid receptor promoter region. Metab Brain Dis 24, 615–627 (2009). https://doi.org/10.1007/s11011-009-9163-4

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  • DOI: https://doi.org/10.1007/s11011-009-9163-4

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