Stress-induced neuroinflammatory priming: A liability factor in the etiology of psychiatric disorders.
Stress-induced neuroinflammatory priming: A liability factor in the etiology of psychiatric disorders.
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DOI：
10.1016/j.ynstr.2015.12.004
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发表时间：
2016-10
影响因子：
5
通讯作者：
Maier, Steven F
中科院分区：
文献类型：
--
作者：
Frank, Matthew G;Weber, Michael D;Watkins, Linda R;Maier, Steven F
应激和糖皮质激素（GCs）被普遍认为具有抗炎作用，然而近年来，应激和糖皮质激素被发现在神经炎症过程中发挥许可效应（免疫启动）。这种启动现象的特征是先前的应激或GC暴露增强了对随后免疫挑战的神经炎症反应。这里讨论了大量证据，支持压力和gc的这种允许效应。根据这一证据，我们提出了一种神经炎症启动机制，涉及大脑中涉及危险相关分子模式（HMGB-1）和炎症小体（NLRP3）的信号级联，导致神经炎症反应被夸大或放大，随后，该反应的生理和行为后遗症（即疾病）被放大。最后，我们探讨了应激源诱导的神经免疫微环境敏化可能使个体易患精神疾病的概念，目前认为大脑中夸大的先天免疫/炎症反应在其中起关键作用。
Stress and glucocorticoids (GCs) have universally been considered to be anti-inflammatory, however in recent years, stress and GCs have been found to exert permissive effects (immunological priming) on neuroinflammatory processes. This phenomenon of priming is characterized by prior stress or GC exposure potentiating the neuroinflammatory response to a subsequent immune challenge. A considerable body of evidence is discussed here that supports this permissive effect of stress and GCs. In light of this evidence, a mechanism of neuroinflammatory priming is proposed involving a signal cascade in the brain involving danger-associated molecular patterns (HMGB-1) and inflammasomes (NLRP3), which results in an exaggerated or amplified neuroinflammatory response and subsequently, the amplification of the physiological and behavioral sequelae of this response (i.e. sickness). Finally, we explore the notion that stressor-induced sensitization of the neuroimmune microenvironment may predispose individuals to psychiatric disorders, in which exaggerated innate immune/inflammatory responses in the brain are now thought to play a key role.