Objective To evalaute the role of hippocampal ubiquinol cytochrome C reductase core protein 1(UQCRC1)in cognitive dysfunction after global cerebral ischemia(GCI)in mice.Methods Forty SPF healthy male C57BL/6J mice,aged 12 weeks,weighing 22-26 g,were selected,and 20 of them were divided into 2 groups(n=10 each)using a random number table method:sham operation group and GCI1 group.The other 20 mice were divided into 2 groups(n=10 each)by the random number table meth-od:GCI2 group and GCI+UQCRC1 overexpression group(GCI+UQCRC1 group).In Sham group,the skin was directly sutured after exposing both common carotid arteries.Global cerebral ischemia was induced by occlusion of bilateral common carotid arteries for 20 min in GCI1,GCI2 and GCI+UQCRC1 group,and lentivirus VSVG-Lentivirus-hSyn-EGFP-P2A-UQCRC1-WPRE-pA 500 nl was injected into the bilateral hip-pocampus at 2 weeks before developing the model in GCI+UQCRC1 group.The novel object recognition task was carried out on the 2nd day following completion of model development,and the percentage of time spent exploring the novel object was calculated.The fear conditioning test was carried out on days 3-4 after com-pletion of model development,and the freezing time was recorded.Morris water maze test was performed on days 5-10 after completion of model development,and the escape latency and time spent in the target quad-rant were recorded.After the Morris water maze test,the expression of UQCRC1 in the hippocampal CA1 re-gion was detected by immunofluorescence and Western blot.Results Compared with Sham group,the per-centage of time spent exploring the novel object was significantly decreased,the percentage of freezing time in training and test stages was decreased,the escape latency on days 6-9 was prolonged,the percentage of time spent in the target quadrant was decreased,and the expression of UQCRC1 in the hippocampal CA1 was down-regulated in GCI1 group(P＜0.05).Compared with GCI2 group,the percentage of time spent ex-ploring the novel object was significantly increased,the percentage of freezing time in training and test sta-ges was increased,the escape latency on days 6-9 was shortened,the percentage of time spent in the target quadrant was increased,and the expression of UQCRC1 in the hippocampal CA1 region was up-regulated in GCI+UQCRC1 group(P＜0.05).Conclusions Hippocampal UQCRC1 is involved in the process of cogni-tive dysfunction following GCI in mice.
关键词
电子传递复合物Ⅲ/脑缺血/认知功能障碍
Key words
Electron transport complex Ⅲ/Brain ischemia/Cognitive dysfunction
万方数据