Social interaction modulates the neuroinflammatory response to global cerebral ischemia in male mice
Social interaction modulates the neuroinflammatory response to global cerebral ischemia in male mice
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DOI：
10.1016/j.brainres.2017.08.008
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发表时间：
2017-10-15
期刊：
影响因子：
2.9
通讯作者：
DeVries, A. Courtney
中科院分区：
文献类型：
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作者：
Gaudier-Diaz, Monica M.;Zhang, Ning;DeVries, A. Courtney
社会孤立是心脑血管疾病的一个危险因素，尽管其潜在的机制仍未得到详细说明。考虑到小胶质细胞被应激源敏化的可能性及其在神经炎症中的作用，我们假设社会隔离启动了小胶质细胞，导致了对实验性脑缺血的夸大神经免疫反应。首先，主要组织相容性复合体II(MHC II)基因的表达，一个小胶质细胞启动的指标，在社会隔离或配对居住的小鼠之间进行了比较。MHC II在社交隔离小鼠的海马区和大脑皮层增加，这提示隔离诱导了小胶质细胞的启动。在实验2中，隔离和配对饲养的小鼠经历了类似于8分钟的全脑缺血。与假手术对照组相比，单纯缺血组和成对缺血组大鼠海马区肿瘤坏死因子-α和白介素6的mRNA表达均显著增加。海马区IL-1β(IL-1β)和皮质干扰素-α(IL-1β)、IL-1β和IL-6的表达在缺血24 h后显著增加，但配对饲养的小鼠与对照组相比无显著差异。与对照组相比，缺血诱导的小胶质细胞胞体面积和电离钙结合适配器分子1(Iba-1)阳性染色面积百分比的增加也在隔离小鼠中观察到，但在配对小鼠中没有观察到。在实验3中，来自社会隔离和配对居住的小鼠的大脑切片进行了15分钟的氧糖剥夺(OGD)，这是一种体外脑缺血模型。在OGD后，IL-6基因的表达仅在社交隔离的小鼠的海马区显著升高，表明缺血前的隔离足以调节神经炎性反应。综上所述，这些数据表明，小胶质细胞的启动可能是社交隔离对脑缺血结局产生不利影响的一个可能机制。(C)2017爱思唯尔B.V.保留所有权利。
Social isolation is a risk factor for cardiovascular and cerebrovascular diseases, although the underlying mechanisms remain underspecified. Considering the potential of microglia to become sensitized by stressors and their role in neuroinflammation, we hypothesized that social isolation primes microglia, resulting in an exaggerated neuroimmune response to experimental cerebral ischemia. First, major histocompatibility complex II (MHC II) gene expression, an indicator of microglial priming, was compared between mice that were socially isolated or pair-housed. MHC II increased in the hippocampus and cortex of socially isolated mice, which is suggestive of isolation-induced microglial priming. In experiment 2, isolated and pair-housed mice underwent similar to 8 min of global cerebral ischemia. Hippocampal mRNA expression of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) was significantly increased among both isolated and pair-housed ischemia groups relative to sham controls. Hippocampal expression of interleukin 1 beta (IL-1 beta and cortical INF-alpha, IL-1 beta and IL-6, were significantly increased 24-h postischemia in isolated mice, but not pair-housed mice, relative to controls. Ischemia-induced increases in microglial cell body area and percent area fraction of ionized calcium binding adaptor molecule 1 (Iba-1) positive staining were also observed in isolated, but not pair-housed mice, relative to controls. For experiment 3, brain sections from socially isolated and pair-housed mice underwent 15 min of oxygen glucose deprivation (OGD), an ex vivo model of cerebral ischemia. IL-6 gene expression was significantly elevated following OGD only in hippocampi from mice that had been socially isolated, indicating that isolation prior to ischemia is sufficient to modulate the neuroinflammatory response. Together, these data suggest microglial priming as a possible mechanism underlying the detrimental effects of social isolation on cerebral ischemia outcome. (C) 2017 Elsevier B.V. All rights reserved.