The neurobiology of stress: from serendipity to clinical relevance

The hormones and other physiological agents that mediate the effects of str ess on the body have protective and adaptive effects in the short run and y et can accelerate pathophysiology when they are over-produced or mismanaged . Here we consider the protective and damaging effects of these mediators a s they relate: to the immune system and brain. 'Stress' is a principle focu s. but this term is rather imprecise. Therefore, the article begins by noti ng two new terms, allostasis and allostatic load that are intended to suppl ement and clarify the meanings of 'stress' and 'homeostasis'. For the immun e system, acute stress enhances immune function whereas chronic stress supp resses it. These effects can be beneficial for some types of immune respons es and deleterious for others. A key mechanism involves the stress-hormone dependent translocation of immune cells in the blood to tissues and organs where an immune defense is needed. For the brain, acute stress enhances the memory of events that are potentially threatening to the organism. Chronic stress, on the other hand, causes adaptive plasticity in the brain, in whi ch local neurotransmitters as well as systemic hormones interact to produce structural as well as functional changes, involving the suppression of ong oing neurogenesis in the dentate gyrus and remodelling of dendrites in the Ammon's horn. Under extreme conditions only does permanent damage ensue. Ad renal steroids tell only part of the story as far as how the brain adapts, or shows damage, and local tissue modulators - cytokines for the immune res ponse and excitatory amino acid neurotransmitters for the hippocampus. More over. comparison of the effects of experimenter-applied stressors and psych osocial stressors show that what animals do to each other is often more pot ent than what experimenters do to them. And yet, even then, the brain is re silient and capable of adaptive plasticity. Stress-induced structural chang es in brain regions such as the hippocampus have clinical ramifcations for disorders such as depression. post-traumatic stress disorder and individual differences in the aging process. (C) 2000 Elsevier Science B.V. All right s reserved.