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  • The neurobiology of stress: from serendipity to clinical relevance

    Bruce S. McEwen

    Abstract The hormones and other physiological agents that mediate the effects of stress on the body have protective and adaptive effects in the short run and yet can accelerate pathophysiology when they are over-produced or mismanaged. Here we consider the protective and damaging effects of these mediators as they relate to the immune system and brain. ‘Stress’ is a principle focus, but this term is rather imprecise. Therefore, the article begins by noting two new terms, allostasis and allostatic load that are intended to supplement and clarify the meanings of ‘stress’ and ‘homeostasis’. For the immune system, acute stress enhances immune function whereas chronic stress suppresses it. These effects can be beneficial for some types of immune responses 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 which local neurotransmitters as well as systemic hormones interact to produce structural as well as functional changes, involving the suppression of ongoing neurogenesis in the dentate gyrus and remodelling of dendrites in the Ammon’s horn. Under extreme conditions only does permanent damage ensue. Adrenal 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 response and excitatory amino acid neurotransmitters for the hippocampus. Moreover, comparison of the effects of experimenter-applied stressors and psychosocial stressors show that what animals do to each other is often more potent than what experimenters do to them. And yet, even then, the brain is resilient and capable of adaptive plasticity. Stress-induced structural changes in brain regions such as the hippocampus have clinical ramifications for disorders such as depression, post-traumatic stress disorder and individual differences in the aging process.  2000 Elsevier Science B.V. All rights reserved.

    Keywords: Stress; Homeostasis; Allostasis; Immune function; Adaptive plasticity; Hippocampus; Dendrite; Neurotransmitter; Glucocorticoid; Adrenalectomy; Adrenal steroid; Learning; Memory; Cognitive function; Psychiatric disorder.

    mcewen2000.pdf

  • Physiology and Neurobiology of Stress and Adaptation: Central Role of the Brain

    BRUCE S. McEWEN

    Alfred E. Mirsky Professor and Head, Harold and Margaret Milliken Hatch, Laboratory of Neuroendocrinology, The Rockefeller University, New York.

    The brain is the key organ of the response to stress because it determines what is threatening and, therefore, potentially stressful, as well as the physiological and behavioral responses which can be either adaptive or damaging. Stress involves two-way communication between the brain and the cardiovascular, immune, and other systems via neural and endocrine mechanisms. Beyond the “flight-or-fight” response to acute stress, there are events in daily life that produce a type of chronic stress and lead over time to wear and tear on the body (“allostatic load”). Yet, hormones associated with stress protect the body in the short-run and promote adaptation (“allostasis”). The brain is a target of stress, and the hippocampus was the first brain region, besides the hypothalamus, to be recognized as a target of glucocorticoids. Stress and stress hormones produce both adaptive and maladaptive effects on this brain region throughout the life course. Early life events influence life-long patterns of emotionality and stress responsiveness and alter the rate of brain and body aging. The hippocampus, amygdala, and prefrontal cortex undergo stress-induced structural remodeling, which alters behavioral and physiPhysiol

    Rev 87: 873–904, 2007; doi:10.1152/physrev.00041.2006. www.prv.org 0031-9333/07 Copyright © 2007 the American Physiological Society 873 on June 3, 2012 physrev.physiology.org Downloaded from ological responses. As an adjunct to pharmaceutical therapy, social and behavioral interventions such as regular physical activity and social support reduce the chronic stress burden and benefit brain and body health and resilience.

    mcewen2007.pdf

  • COGNITIVE NEUROSCIENCE OF HUMAN SOCIAL BEHAVIOUR

    Ralph Adolphs

    We are an intensely social species — it has been argued that our social nature defines what makes us human, what makes us conscious or what gave us our large brains. As a new field, the social brain sciences are probing the neural underpinnings of social behaviour and have produced a banquet of data that are both tantalizing and deeply puzzling. We are finding new links between emotion and reason, between action and perception, and between representations of other people and ourselves. No less important are the links that are also being established across disciplines to understand social behaviour, as neuroscientists, social psychologists, anthropologists, ethologists and philosophers forge new collaborations.

    Adolphs R.-Cognitive Neuroscience Of Human Social Behaviour (2003).pdf