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Stress and the brain: from adaptation to disease
E Ron de Kloet1, Marian Joëls, Florian Holsboer
1Department of Medical Pharmacology, Leiden Amsterdam Center for Drug Research and Leiden University Medical Center, Gorlaeus Laboratories, Leiden University, PO Box 9502, 2300 RA Leiden, The Netherlands. e.kloet@lacdr.leidenuniv.nl
Nature Reviews. Neuroscience
|May 14, 2005
Summary
Stress response involves brain neuropeptide systems and adrenal corticosteroid hormones, which regulate neuronal adaptation. Imbalances in this system can lead to stress-related brain diseases in susceptible individuals.
Area of Science:
- Neuroendocrinology
- Molecular Psychiatry
- Behavioral Neuroscience
Background:
- The brain activates neuropeptide systems in response to stress, leading to corticosteroid hormone release.
- Corticosteroids act as transcriptional regulators via nuclear receptors, controlling neuronal and network responses for behavioral adaptation.
Purpose of the Study:
- To investigate the role of corticosteroid hormone signaling in stress response and behavioral adaptation.
- To identify genetic factors contributing to vulnerability to stress-related brain diseases.
Main Methods:
- Analysis of neuropeptide-secreting systems and corticosteroid hormone feedback loops.
- Investigation of nuclear receptor binding and transcriptional regulation by corticosteroids.
- Identification of candidate susceptibility genes for stress-related disorders.
Main Results:
- Corticosteroids function as a binary switch, controlling adaptive neuronal and network responses.
- Imbalances in corticosteroid signaling can predispose individuals to brain disease after stress.
- Candidate genes are being identified as markers for predicting vulnerable phenotypes.
Conclusions:
- The corticosteroid system plays a critical role in mediating the brain's response to stress and adaptation.
- Genetic predisposition significantly influences the impact of stress on brain health.
- Identifying susceptibility genes is crucial for predicting and potentially preventing stress-related brain diseases.