The neurobiology of stress: from serendipity to clinical relevance
The neurobiology of stress: from serendipity to clinical relevance
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DOI：
10.1016/s0006-8993(00)02950-4
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发表时间：
2000-12-15
期刊：
影响因子：
2.9
通讯作者：
McEwen, BS
中科院分区：
文献类型：
--
作者：
McEwen, BS
激素和其他生理因子介导压力对身体的影响，在短期内具有保护和适应作用，但当它们过量产生或管理不当时，可能会加速病理生理。在这里，我们考虑这些介质的保护和破坏作用，因为它们与免疫系统和大脑有关。“压力”是一个原则焦点。但是这个术语相当不精确。因此，本文首先指出了两个新术语，即“适应平衡”和“适应负荷”，它们旨在补充和澄清“压力”和“体内平衡”的含义。对免疫系统来说，急性应激增强免疫功能，而慢性应激则抑制免疫功能。这些影响可能对某些类型的免疫反应有益，对其他类型的免疫反应有害。一个关键的机制涉及到血液中免疫细胞的应激激素依赖易位到需要免疫防御的组织和器官。对于大脑来说，急性压力增强了对生物体潜在威胁事件的记忆。另一方面，慢性应激引起大脑的适应性可塑性，其中局部神经递质和全身激素相互作用产生结构和功能变化，包括抑制齿状回正在进行的神经发生和阿蒙角树突的重塑。只有在极端条件下才会造成永久性损伤。至于大脑如何适应或显示损伤，以及局部组织调节剂——免疫反应的细胞因子和海马体的兴奋性氨基酸神经递质，肾上腺类固醇只能说明部分问题。此外。实验人员施加的压力源和社会心理压力源的影响比较表明，动物对彼此的影响往往比实验人员对它们的影响更大。然而，即便如此，大脑是有弹性的，能够适应可塑性。在诸如海马体之类的大脑区域中，压力引起的结构变化对抑郁症等疾病具有临床影响。创伤后应激障碍与衰老过程中的个体差异。(C) 2000 Elsevier Science B.V.版权所有
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 ramifcations for disorders such as depression. post-traumatic stress disorder and individual differences in the aging process. (C) 2000 Elsevier Science B.V. All rights reserved.