Impact of Stress on the Brain: Pathology, Treatment and Prevention.
Impact of Stress on the Brain: Pathology, Treatment and Prevention.
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压力对大脑的影响：病理学、治疗和预防。
DOI：
10.1038/npp.2015.306
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
Smoller,JordanW
中科院分区：
文献类型：
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作者：
Ressler,KerryJ;Smoller,JordanW
我们很高兴地介绍2016年神经心理药理学评论版，它侧重于我们对压力对大脑影响的理解的进展：从病理到回路，从治疗到预防。来自遗传学、表观遗传学、神经回路和代际模型、动物模型和神经影像学的新数据都表明，压力以各种动态且通常持久的方式影响大脑。这些过程对病理发育风险的影响尤为显著。下面我们简要地概述了这里所涉及的主题的广度，以及它们是如何整合在一起的，并共同推进我们对神经回路和调解压力和恐惧反应的过程的整体理解。这个问题从探索应激对神经元结构和功能的影响开始。这一领域对应激和下丘脑-垂体-肾上腺（HPA）轴功能对树突回缩和脊柱密度降低的影响产生了许多有趣的见解，这些都是细胞功能和可塑性下降的细胞指标（McEwen等人，2016）。在此基础上，Antoine Besnard和Amar Sahay详细介绍了我们对成人大脑内，特别是海马体内神经发生的最新理解，以及这一过程如何介导对离散记忆事件的区分。此外，在压力模型中，这种神经发生似乎受到损害，部分原因是海马神经发生减少导致压力和恐惧泛化（Besnard和Sahay， 2016）。接下来的章节将重点关注在过去十年中发展得特别好的压力的一个方面——恐惧调节及其潜在的神经回路。Michael Fanselow探讨了先前的压力敏化对后来增强的恐惧反应的影响（Perusini等人，2016），提供了一个潜在的重要模型，有助于深入了解为什么先前的压力史会增加新创伤暴露后PTSD的可能性。下一章以这些观点为基础，研究压力如何影响情境恐惧学习，特别是与压力反应和恐惧系统的失调有关，正如各种焦虑症所发生的那样（Maren和Holmes， 2016）。恐惧是如何被压力调节的，人们开始从不同的层面来理解，包括神经回路和潜在的分子机制。在过去的几年里，一组特别有趣的发现揭示了内源性大麻素系统是如何参与恐惧的消除和调节压力反应的，正如本节末尾详细回顾的那样
We are pleased to present the 2016 Neuropsycho-pharmacology Reviews Edition, which focuses on advances in our understanding of the impact of stress on the brain: from pathology to circuits, treatment to prevention. Emerging data from genetics, epigenetics, neural circuit and intergenerational models, animal models, and neuroimaging all suggest that stress affects the brain in a variety of dynamic and often long-lasting ways. The effects of these processes on developmental risk for pathology are particularly notable. Below we briefly outline the breadth of topics covered herein, as well as how they are integrated and together advance our overall understanding of the neural circuits and processes mediating the stress and fear responses. The issue begins with an exploration of the effects of stress on neuronal structure and function. This area has led to a number of fascinating insights into the effects of stress and hypothalamic–pituitary–adrenal (HPA) axis function on dendritic retraction and decreased spine density—all cellular measures of decreased cellular functioning and plasticity (McEwen et al, 2016). Following on this, Antoine Besnard and Amar Sahay detail our up-to-date understanding of neurogenesis within the adult brain, particularly within the hippocampus, and how this process may mediate discrimination of discrete memory events. Furthermore, in stress models, this neurogenesis appears to be impaired, in part resulting in the stress-and fear-generalization that occurs with diminished hippocampal neurogenesis (Besnard and Sahay, 2016). The next chapters focus on an aspect of stress that has been particularly well developed in the last decade—fear regulation and its underlying neural circuity. Michael Fanselow explores the effect of prior stress sensitization on later enhanced fear responses (Perusini et al, 2016), providing a potentially important model helping to provide insight into why a history of prior stress increases the likelihood of PTSD following new trauma exposure. The following chapter builds on these ideas by examining how stress affects contextual fear learning, particularly related to dysregulation of the stress response and fear systems, as occurs in a variety of anxiety disorders (Maren and Holmes, 2016). How fear is modulated by stress is beginning to be understood at a variety of levels, including both neural circuitry and underlying molecular mechanisms. A particularly interesting set of findings over the past few years has revealed how the endogenous cannabinoid system is involved in both extinction of fear and in modulating the stress response, as reviewed in detail at the end of this section