Stress in the brain.
Part I (first section) reports about research in the period 1964-1976, when the seminal observations were made on which today's concept of corticosteroid action on the brain is based. These key observations concern the discovery of nuclear corticosterone receptors in the limbic brain that mediate control over neuronal circuits underlying hypothalamic-pituitary-adrenal activity and behavioural adaptation. Part II (second section) covers the period of 1977-1989. It is about some aspects of the neuropeptide concept, the implementation of micro-neurochemistry using the "Palkovits punch", and the application of in vitro autoradiography. Vasopressin and oxytocin receptors were identified and their implication in behaviour was examined using the song control of the canary bird as a model system. Two distinct nuclear receptor types for corticosteroids were identified: mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) which mediate in a coordinate manner the steroid control of hypothalamus-pituitary-adrenal activity and behaviour. Part III (third section) is from 1990 up to 2000. Focus is on the balance of MR- and GR-mediated actions in control of homeostasis as a determinant of health and disease. MR operates in pro-active mode to prevent homeostatic disturbance, while additional GR activation promotes in reactive fashion recovery after stress. An imbalance in MR and GR underlies behavioural deficits and neuroendocrine disturbances increasing vulnerability for stress-related brain disorders. The complete hippocampal genome is screened for corticosteroid responsive genes, which are potential targets for drugs promoting restorative capacity still present in the diseased brain.
de Kloet
E R
ER
Department 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
D000305:Adrenal Cortex Hormones / Q000502:physiology; D000818:Animals; D001921:Brain / Q000503:physiopathology*; D006801:Humans; D009479:Neuropeptides / Q000502:physiology; D013315:Stress, Psychological / Q000503:physiopathology*
D000305:Adrenal Cortex Hormones; D009479:Neuropeptides