Acute stress induces chronic neuroinflammatory, microglial and behavioral priming: A role for potentiated NLRP3 inflammasome activation.
Acute stress induces chronic neuroinflammatory, microglial and behavioral priming: A role for potentiated NLRP3 inflammasome activation.
复制标题
DOI：
10.1016/j.bbi.2020.05.063
复制
发表时间：
2020-10
期刊：
影响因子：
--
通讯作者：
Maier SF
中科院分区：
文献类型：
--
作者：
Frank MG;Fonken LK;Watkins LR;Maier SF
先前暴露于急性和慢性应激源增强了神经炎症和小胶质细胞促炎反应，以随后的免疫挑战，这表明应激源敏化或引发小胶质细胞。应激诱导的NLRP 3炎性小体引发与这种引发现象有关，然而这些作用的持续时间/持久性尚未研究。在本研究中，我们研究了暴露于单一急性应激源（不可避免的尾休克）是否诱导NLRP 3炎性小体的长期启动以及海马中随后免疫挑战的神经炎症，行为和小胶质细胞促炎反应。在雄性Sprague-Dawley大鼠中，急性应激增强了应激暴露后8天给予免疫激发（脂多糖; LPS）的神经炎症反应（IL-1β、IL-6和NFκBIα）。急性应激还增强了对LPS的促炎细胞因子（IL-1β、IL-6、TNF和NFκBIα）离体反应。在应激后28天也观察到这种应激诱导的小胶质细胞启动。此外，在免疫攻击前8天暴露于应激的动物中，LPS攻击减少了青少年的社会探索，但不减少蔗糖偏好。暴露于急性应激也增加了NLRP 3的基础mRNA水平，并增强了应激后8天的caspase-1 mRNA和蛋白活性的LPS诱导。目前的研究结果表明，急性应激产生了长期的脆弱性，随后的免疫挑战的神经炎症效应，从而增加了与病因炎症成分的应激相关的精神疾病的风险。此外，这些发现表明急性应激可能诱导小胶质细胞中的先天免疫记忆的独特可能性。
Prior exposure to acute and chronic stressors potentiates the neuroinflammatory and microglial pro-inflammatory response to subsequent immune challenges suggesting that stressors sensitize or prime microglia. Stress-induced priming of the NLRP3 inflammasome has been implicated in this priming phenomenon, however the duration/persistence of these effects has not been investigated. In the present study, we examined whether exposure to a single acute stressor (inescapable tailshock) induced a protracted priming of the NLRP3 inflammasome as well as the neuroinflammatory, behavioral and microglial proinflammatory response to a subsequent immune challenge in hippocampus. In male Sprague-Dawley rats, acute stress potentiated the neuroinflammatory response (IL-1β, IL-6, and NFκBIα) to an immune challenge (lipopolysaccharide; LPS) administered 8 days after stressor exposure. Acute stress also potentiated the proinflammatory cytokine response (IL-1β, IL-6, TNF and NFκBIα) to LPS ex vivo. This stress-induced priming of microglia also was observed 28 days post-stress. Furthermore, challenge with LPS reduced juvenile social exploration, but not sucrose preference, in animals exposed to stress 8 days prior to immune challenge. Exposure to acute stress also increased basal mRNA levels of NLRP3 and potentiated LPS-induction of caspase-1 mRNA and protein activity 8 days after stress. The present findings suggest that acute stress produces a protracted vulnerability to the neuroinflammatory effects of subsequent immune challenges, thereby increasing risk for stress-related psychiatric disorders with an etiological inflammatory component. Further, these findings suggest the unique possibility that acute stress might induce innate immune memory in microglia.
登录
查看更多内容
影响因子：
8.7
作者：
Elliott EI;Sutterwala FS
通讯作者：
Sutterwala FS
影响因子：
5.1
作者：
Alcocer-Gomez, Elisabet;Ulecia-Moron, Cristina;Cordero, Mario D.
通讯作者：
Cordero, Mario D.
影响因子：
2.9
作者：
CHOMCZYNSKI, P;SACCHI, N
通讯作者：
SACCHI, N
影响因子：
10.6
作者：
Franklin TC;Wohleb ES;Zhang Y;Fogaça M;Hare B;Duman RS
通讯作者：
Duman RS
DOI：
10.1073/pnas.2234031100
发表时间：
2003-11-11
影响因子：
11.1
作者：
Ekdahl, CT;Claasen, JH;Lindvall, O
通讯作者：
Lindvall, O