Differential effects of stress on microglial cell activation in male and female medial prefrontal cortex.
Differential effects of stress on microglial cell activation in male and female medial prefrontal cortex.
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DOI：
10.1016/j.bbi.2015.10.003
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发表时间：
2016-02
期刊：
影响因子：
--
通讯作者：
Wellman CL
中科院分区：
文献类型：
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作者：
Bollinger JL;Bergeon Burns CM;Wellman CL
男女对与压力有关的心理障碍，包括创伤后应激障碍和抑郁症的易感性不同。内侧前额叶皮质（mPFC）功能障碍与许多这些疾病有关。慢性应激以性别依赖的方式影响mPFC，差异重塑树突形态和破坏男性和女性的前额介导的行为。慢性束缚应激诱导雄性大鼠mPFC中小胶质细胞活化，反映在改变的小胶质细胞形态和免疫因子表达。无压力的女性表现出增加的小胶质细胞分支在几个大脑区域相比，男性，这表明提高基础激活和潜在的性别依赖性的影响，压力对小胶质细胞激活。因此，我们评估了小胶质细胞的密度和分支在mPFC的边缘前区，和免疫相关基因在背侧mPFC在雄性和雌性大鼠急性或慢性束缚应激。对照组大鼠不受应激。在束缚的最后一天，收集大脑用于qPCR或使用Iba-1免疫组织化学观察小胶质细胞。将mPFC中的小胶质细胞分为分支型、启动型、反应型和变形虫型，并进行体视学计数。还使用qPCR评估了小胶质细胞相关基因（MHCII、CD 40、IL 6、CX 3CL 1和CX 3CR 1）的表达。未受压力的女性表现出更大比例的引发分支小胶质细胞相对于男性，随着CX 3CL 1-CX 3CR 1表达增高。急性和慢性束缚应激降低了女性中引发的分支小胶质细胞和小胶质细胞CD 40表达的比例，但没有显着改变男性中的小胶质细胞活化。小胶质细胞激活的性别差异可能有助于男性与女性的mPFC结构和功能的压力的差异影响。
Susceptibility to stress-linked psychological disorders, including post-traumatic stress disorder and depression, differs between men and women. Dysfunction of medial prefrontal cortex (mPFC) has been implicated in many of these disorders. Chronic stress affects mPFC in a sex-dependent manner, differentially remodeling dendritic morphology and disrupting prefrontally mediated behaviors in males and females. Chronic restraint stress induces microglial activation, reflected in altered microglial morphology and immune factor expression, in mPFC in male rats. Unstressed females exhibit increased microglial ramification in several brain regions compared to males, suggesting both heightened basal activation and a potential for sex-dependent effects of stress on microglial activation. Therefore, we assessed microglial density and ramification in the prelimbic region of mPFC, and immune-associated genes in dorsal mPFC in male and female rats following acute or chronic restraint stress. Control rats were left unstressed. On the final day of restraint, brains were collected for either qPCR or visualization of microglia using Iba-1 immunohistochemistry. Microglia in mPFC were classified as ramified, primed, reactive, or amoeboid, and counted stereologically. Expression of microglia-associated genes (MHCII, CD40, IL6, CX3CL1, and CX3CR1) was also assessed using qPCR. Unstressed females showed a greater proportion of primed to ramified microglia relative to males, alongside heightened CX3CL1-CX3CR1 expression. Acute and chronic restraint stress reduced the proportion of primed to ramified microglia and microglial CD40 expression in females, but did not significantly alter microglial activation in males. This sex difference in microglial activation could contribute to the differential effects of stress on mPFC structure and function in males versus females.