Chronic Cerebral Ischemia Induces Downregulation of A1 Adenosine Receptors During White Matter Damage in Adult Mice
Chronic Cerebral Ischemia Induces Downregulation of A1 Adenosine Receptors During White Matter Damage in Adult Mice
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DOI：
10.1007/s10571-015-0208-4
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发表时间：
2015-11-01
影响因子：
4
通讯作者：
Huang, Wen
中科院分区：
文献类型：
--
作者：
Cheng, Pengfei;Ren, Yifei;Huang, Wen
A1腺苷受体（A1ARs）在慢性脑缺血条件下白质中的作用尚不清楚。本实验采用右单侧颈总动脉闭塞术（rUCCAO）建立小鼠慢性脑缺血模型。免疫反应和免疫组织化学分别观察A1AR和蛋白脂蛋白（白质髓鞘形成标志物）在胼胝体中的表达。ELISA法检测促炎白细胞介素-1 β (IL-1 β)和抗炎白细胞介素-10 （IL-10）水平。Morris水迷宫试验检测认知功能障碍。与假对照组相比，rUCCAO组A1AR表达分别在第2、4、6周显著降低。rUCCAO组IL-10水平在第6周显著下降，IL-1 β表达无明显变化。在第2、4、6周，rUCCAO组PLP表达明显降低。此外，rUCCAO组在第4周和第6周Morris水迷宫测试的潜伏期显著增加，而在第2周、第4周和第6周，rUCCAO组的平台位置穿越次数显著减少。总之，本研究首次证实慢性脑缺血诱导A1AR下调并抑制IL-10的产生，这可能在缺血性脑白质病变的神经病理机制中起关键作用。这些数据将有助于未来研究制定有效的治疗策略缺血性白质病变。
The role of A1 adenosine receptors (A1ARs) in the white matter under chronic cerebral ischemic conditions remains unclear. Here, we used right unilateral common carotid artery occlusion (rUCCAO) to construct a chronic cerebral ischemic mouse model. A1AR expression and proteolipid protein (PLP, a marker of white matter myelination) in the corpus callosum were observed by immunoreaction and immunohistochemistry, respectively. Pro-inflammatory interleukin-1 beta (IL-1 beta) and anti-inflammatory interleukin-10 (IL-10) levels were determined by ELISA. The Morris water maze test was employed to detect cognitive impairment. A1AR expression significantly decreased in the rUCCAO group as compared with the sham control group on weeks 2, 4, and 6, respectively. IL-10 levels in the rUCCAO group significantly declined on week 6, while there was no significant change in IL-1 beta expression. PLP expression significantly decreased in the rUCCAO group on weeks 2, 4, and 6. Moreover, latency time for the Morris water maze test significantly increased in the rUCCAO group on weeks 4 and 6, while the number of platform location crossing significantly decreased in the rUCCAO group on weeks 2, 4, and 6. In conclusion, this study provides the first evidence that chronic cerebral ischemia appears to induce A1AR downregulation and inhibition of IL-10 production, which may play key roles in the neuropathological mechanisms of ischemic white matter lesions. These data will facilitate future studies in formulating effective therapeutic strategies for ischemic white matter lesions.