Brain Corticosteroid Receptor Function in Response to Psychosocial Stressors

  • E.R de Kloet
  • N.A. Datson
  • Y. Revsin
  • D.L. Champagne
  • M.S. Oitzl

Abstract

A fundamental question in the neuroendocrinology of stress and adaptation is how stress mediators that are crucial for resilience and health can change into harmful signals enhancing vulnerability to disease. To address this question, we focus in the rodent on corticosterone as the end product of the hypothalamic-pituitary-adrenal (HPA) axis, which coordinates the behavioural and physiological response to stressors. The action of corticosterone ismediated bymineralocorticoid (MR)and glucocorticoid receptors (GR) that are abundantly expressed in neurons of the limbic hippocampus, amygdala and prefrontal cortex. The receptors are transcription factors regulating gene transcription but recently – much to our surprise – these nuclear receptors also were discovered tomediate rapid, non-genomic action on glutamate transmission.MR participates in initial stress reactions important for appraisal and coping processes, whereas management of the later adaptive phase primarily depends on GR. Gene variants of MR and GR have been identified. Moreover, the expression of MR and GR shows enduring epigenetic changes in response to early life experience. Both gene variants and the altered expression of MR and GR have lasting consequences for stress responsiveness, cognitive performance and emotional arousal in later life. In conclusion, an imbalance in stress mediators caused by genetic factors and early life experience is a characteristic feature of a phenotype vulnerable for later life stressors. This concept calls for recovery of the MR/GR balance as a therapeutic strategy to promote the resilience that is still present in the diseased brain.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2008

Authors and Affiliations

  • E.R de Kloet
    • 1
  • N.A. Datson
    • 1
  • Y. Revsin
    • 1
  • D.L. Champagne
    • 1
  • M.S. Oitzl
    • 1
  1. 1.Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research and LeidenUniversity Medical CenterLeidenNetherlands

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