Central metabolite changes and activation of microglia after peripheral interleukin-2 challenge
Central metabolite changes and activation of microglia after peripheral interleukin-2 challenge
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外周白细胞介素 2 攻击后中枢代谢变化和小胶质细胞激活
DOI：
10.1016/j.bbi.2011.09.011
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Pawlak C.R.
中科院分区：
文献类型：
--
作者：
Schneider P;Weber-Fahr W;Schweinfurth N;Ho Y.J;Sartorius A;Spanagel R;Pawlak C.R.
白细胞介素(IL)-2通过活化t细胞的增殖调节免疫反应，并对中枢神经系统（CNS）产生影响。除了具有显著的神经行为作用外，IL-2还被认为对各种精神疾病有影响。IL-2的免疫-中枢神经系统通讯尚不清楚，但提示小胶质细胞是IL-2的来源和靶点。在这里，我们分析了外周IL-2攻击后脑代谢物的变化，并检查了小胶质细胞在介导这些影响中的作用。在9.4T扫描仪上通过磁共振波谱（MRS）评估大鼠前额皮质（PFC）和海马的基线代谢物水平。7天后，在单次注射IL-2 （2.5μg/kg）后再次扫描动物，然后在升高的正迷宫上测试IL-2诱导的脑代谢物与焦虑测量的相关性。在另一个实验中，检测CD25+小胶质细胞。另一组大鼠分别注射IL-2或对照物，解剖PFC和海马，进行荧光活化细胞分选（FACS）分析。个体内部研究设计的MRS扫描显示分析区域的肌醇显著增加。在海马体中发现了焦虑样测量和肌醇（小胶质细胞活动的标志）的显著相关性。FACS分析显示，与对照组相比，海马中CD25+小胶质细胞显著增加。这些结果支持小胶质细胞在免疫-中枢神经系统通讯和外周IL-2的作用中作为中介的作用。
Interleukin (IL)-2 regulates the immune response through the proliferation of activated T-cells and also exerts effects on the central nervous system (CNS). Alongside having marked neurobehavioral effects, IL-2 has been suggested to impact on various psychiatric disorders. The immune-CNS communication of IL-2 remains unclear, although, it is suggested that microglia are the source and target of IL-2. Here, we analyzed changes in brain metabolites following a peripheral IL-2 challenge and examined the contribution of microglia in mediating these effects. Rats were assessed by magnetic resonance spectroscopy (MRS) in a 9.4T scanner for baseline metabolite levels in the prefrontal cortex (PFC) and the hippocampus. After 7days animals were scanned again following a single injection of IL-2 (2.5μg/kg) and then tested on the elevated plus-maze for the correlation of IL-2-induced brain metabolites and measures of anxiety. In another experiment CD25+microglia cells were determined. A separate group of rats was injected either with IL-2 or vehicle, and afterward the PFC and hippocampus were dissected and fluorescence activated cell sorting (FACS) analysis was performed. The MRS scans in the intra-individual study design showed a significant increase in myo-inositol in the analyzed regions. A significant correlation of anxiety-like measures and myo-inositol, a marker for microglia activity, was found in the hippocampus. The FACS analysis showed a significant increase in CD25+microglia in the hippocampus compared to controls. The results support the role of microglia as a mediator in the immune-CNS communication and the effects of peripheral IL-2.
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作者：
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期刊：
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