Stress and the brain: From adaptation to disease

ER de Kloet*, M Joels, F Holsboer

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

2896 Citations (Scopus)

Abstract

In response to stress, the brain activates several neuropeptide-secreting systems. This eventually leads to the release of adrenal corticosteroid hormones, which subsequently feed back on the brain and bind to two types of nuclear receptor that act as transcriptional regulators. By targeting many genes, corticosteroids function in a binary fashion, and serve as a master switch in the control of neuronal and network responses that underlie behavioural adaptation. In genetically predisposed individuals, an imbalance in this binary control mechanism can introduce a bias towards stress-related brain disease after adverse experiences. New candidate susceptibility genes that serve as markers for the prediction of vulnerable phenotypes are now being identified.

Original languageEnglish
Pages (from-to)463-475
Number of pages13
JournalNature reviews neuroscience
Volume6
Issue number6
DOIs
Publication statusPublished - Jun-2005
Externally publishedYes

Keywords

  • CORTICOTROPIN-RELEASING HORMONE
  • LONG-TERM POTENTIATION
  • GLUCOCORTICOID-RECEPTOR GENE
  • COMBINED DEXAMETHASONE/CRH TEST
  • HIPPOCAMPAL PYRAMIDAL NEURONS
  • MEDIAL PREFRONTAL CORTEX
  • PITUITARY-ADRENAL AXIS
  • RAT DENTATE GYRUS
  • MINERALOCORTICOID-RECEPTOR
  • MAJOR DEPRESSION

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