Stress and aging act through common mechanisms to elicit neuroinflammatory priming.
Stress and aging act through common mechanisms to elicit neuroinflammatory priming.
复制标题
DOI：
10.1016/j.bbi.2018.07.012
复制
发表时间：
2018-10
期刊：
影响因子：
--
通讯作者：
Maier SF
中科院分区：
文献类型：
--
作者：
Fonken LK;Frank MG;Gaudet AD;Maier SF
在动物的一生中，基本的体内平衡功能会有一个漫长的崩溃过程。压力源（心理上和生理上的）可以加速这一过程，并损害多种体内平衡机制。例如，压力和衰老都可以调节神经炎症功能，并引起启动表型，导致免疫激活时神经炎症谱升高。小胶质细胞是大脑中常驻的髓样细胞，它产生“沉默”的免疫机制，以应对压力和衰老，不会立即引起免疫激活；相反，这些变化使细胞为随后的免疫损伤做好了准备。启动小胶质细胞在免疫激活时表现出高炎症反应，可加剧病理。在这篇综述中，我们将探讨应激和衰老诱导的神经炎症启动之间的相似之处。首先，我们将介绍神经免疫学的基本原理。接下来，我们将讨论神经炎症反应在压力和衰老的背景下被启动的证据。我们还将描述细胞特异性对神经炎症启动的贡献，重点是小胶质细胞。最后，将讨论应激和衰老背景下启动的常见机制：这些机制包括糖皮质激素信号传导；危险信号的积累；小胶质细胞的去抑制；以及昼夜节律的崩溃。总的来说，压力和衰老引发的神经炎症启动之间有很多相似之处，这表明压力可能会促进某种形式的早衰。进一步揭示启动机制可能会改善治疗方法，以缓冲压力和衰老引发的行为病理。
Over the course of an animal’s lifespan, there is a protracted breakdown in basic homeostatic functions. Stressors (both psychological and physiological) can accelerate this process and compromise multiple homeostatic mechanisms. For example, both stress and aging can modulate neuroinflammatory function and cause a primed phenotype resulting in a heightened neuroinflammatory profile upon immune activation. Microglia, the brain’s resident myeloid cell, produce “silent” immune machinery in response to stress and aging that does not cause immediate immune activation; rather, these changes prime the cell for a subsequent immune insult. Primed microglia exhibit a hyperinflammatory response upon immune activation that can exacerbate pathology. In this review, we will explore parallels between stress- and aging-induced neuroinflammatory priming. First, we will provide a background on the basic principles of neuroimmunology. Next, we will discuss evidence that neuroinflammatory responses become primed in the context of both stress and aging. We will also describe cell-specific contributions to neuroinflammatory priming with a focus on microglia. Finally, common mechanisms underlying priming in the context of stress and aging will be discussed: these mechanisms include glucocorticoid signaling; accumulation of danger signals; dis-inhibition of microglia; and breakdown of circadian rhythms. Overall, there are multifarious parallels between stress- and aging-elicited neuroinflammatory priming, suggesting that stress may promote a form of premature aging. Further unravelling mechanisms underlying priming could lead to improved treatments for buffering against stress- and aging-elicited behavioral pathologies.
登录
查看更多内容
耦合的增殖和凋亡维持成人大脑中小胶质细胞的快速离职。
影响因子：
8.8
作者：
Askew K;Li K;Olmos-Alonso A;Garcia-Moreno F;Liang Y;Richardson P;Tipton T;Chapman MA;Riecken K;Beccari S;Sierra A;Molnár Z;Cragg MS;Garaschuk O;Perry VH;Gomez-Nicola D
通讯作者：
Gomez-Nicola D
影响因子：
4.2
作者：
Bachstetter, Adam D.;Morganti, Josh M.;Jernberg, Jennifer;Schlunk, Andrea;Mitchell, Staten H.;Brewster, Kaelin W.;Hudson, Charles E.;Cole, Michael J.;Harrison, Jeffrey K.;Bickford, Paula C.;Gemma, Carmelina
通讯作者：
Gemma, Carmelina
DOI：
10.1523/jneurosci.2173-12.2012
发表时间：
2012-10-17
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Barrientos RM;Hein AM;Frank MG;Watkins LR;Maier SF
通讯作者：
Maier SF
影响因子：
15.1
作者：
Abraham, Jayne;Johnson, Rodney W.
通讯作者：
Johnson, Rodney W.
影响因子：
7.3
作者：
Bellavance MA;Rivest S
通讯作者：
Rivest S