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Stress in the brain.

E R de Kloet1

  • 1Department of Medical Pharmacology and Physiology, Leiden/Amsterdam Center for Drug Research, Leiden University Medical Center, Leiden University, P.O. Box 9503, 2300 RA, Leiden, The Netherlands. e.kloet@lacdr.leidenuniv.nl

European Journal of Pharmacology
|October 18, 2000
PubMed
Summary
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Corticosteroid receptors in the brain, mineralocorticoid (MR) and glucocorticoid (GR), regulate stress responses and behavior. Their balanced action is crucial for homeostasis and preventing stress-related brain disorders.

Area of Science:

  • Neuroendocrinology
  • Molecular Psychiatry
  • Behavioral Neuroscience

Background:

  • Seminal observations from 1964-1976 established the concept of corticosteroid action on the brain.
  • Discovery of nuclear corticosterone receptors in the limbic brain mediating hypothalamic-pituitary-adrenal activity and behavioral adaptation.

Purpose of the Study:

  • To review the historical development of understanding corticosteroid action on the brain.
  • To elucidate the roles of mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) in homeostasis and stress.
  • To identify potential therapeutic targets for stress-related brain disorders.

Main Methods:

  • Identification of nuclear corticosterone receptors.
  • Application of micro-neurochemistry (Palkovits punch) and in vitro autoradiography.

Related Experiment Videos

  • Examination of neuropeptide and corticosteroid receptor implications in behavior using avian models.
  • Genome-wide screening of the hippocampus for corticosteroid-responsive genes.

    • Main Results:

    • Two distinct nuclear receptor types, MR and GR, were identified, coordinating steroid control of HPA activity and behavior.
    • MR acts proactively to prevent homeostatic disturbance, while GR reactively promotes recovery from stress.
    • Imbalances in MR and GR function are linked to behavioral deficits, neuroendocrine disturbances, and increased vulnerability to stress-related brain disorders.

    Conclusions:

    • The balance between MR and GR actions is critical for maintaining homeostasis and overall health.
    • Dysregulation of MR/GR pathways contributes to stress-related brain pathologies.
    • Corticosteroid-responsive genes in the hippocampus represent potential targets for novel therapeutic interventions.