Vol 6 n° 2 - Neuroplasticity
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hen we experience a stressful event, the initial response of the brain, body, and behavior is a protective one, and hormones, cytokines, and other mediators, such as the neurotransmitters, are used to survive and adapt to the challenge. However, repeated stressful experiences have deleterious effects, in part because the very same mechanisms that help protect in the short term are now either mismanaged and/or overused.1 And, over weeks, months, and years, the dysregulation and overactivity of these systems can promote changes that appear to be deleterious, and stressful experiences have been reported to be a major risk factor in the occurrence of depressive disorders. For example, in the brain, the overactivity of stress hormones in the blood and endogenous excitatory S t a t e   o f   t h e   a r t 1 1 9 Structural plasticity of the adult brain: how animal models help us understand brain changes in depression and systemic disorders related to depression Bruce S. McEwen, PhD W Copyright © 2004 LLS SAS.  All rights reserved www.dialogues-cns.org The brain interprets experiences and translates them into behavioral and physiological responses. Stressful events are those which are threatening or, at the very least, unexpected and surprising, and the physiological and behavioral responses are intended to promote adaptation via a process called “allostasis.” Chemical mediators of allostasis include cortisol and adrenalin from the adrenal glands, other hormones, and neurotransmitters, the parasympathetic and sym- pathetic nervous systems, and cytokines and chemokines from the immune system. Two brain structures, the amygdala and hippocampus, play key roles in interpreting what is stressful and determining appropriate responses. The hip- pocampus, a key structure for memories of events and contexts, expresses receptors that enable it to respond to gluco- corticoid hormones in the blood. It undergoes atrophy in a number of psychiatric disorders; it also responds to stressors with changes in excitability, decreased dendritic branching, and reduction in number of neurons in the dentate gyrus. The amygdala, which is important for “emotional memories,” becomes hyperactive in posttraumatic stress disorder and depressive illness. In animal models of stress, there is evidence for growth and hypertrophy of nerve cells in the amyg- dala. Changes in the brain after acute and chronic stressors mirror the pattern seen in the metabolic, cardiovascular, and immune systems, that is, short-term adaptation (allostasis) followed by long-term damage (allostatic load), eg, athero- sclerosis, fat deposition obesity, bone demineralization, and impaired immune function. Allostatic load of this kind is seen in major depressive illness and may also be expressed in other chronic anxiety and mood disorders.   © 2004, LLS SAS Dialogues Clin Neurosci. 2004;6:119-133. Keywords:  structural  plasticity;  brain;  allostasis;  allostatic  load;  stress;  depression; anxiety Author  affiliations:  Harold  and  Margaret  Milliken  Hatch  Laboratory  of Neuroendocrinology, The Rockefeller University, New York, NY, USA Address for correspondence: Bruce S. McEwen, PhD, The Rockefeller University, Box 165, 1230 York Avenue, New York, NY 10021, USA.
(e-mail: mcewen@rockefeller.edu)