The role of mTOR signaling pathway on cognitive functions in cerebral ischemia-reperfusion

mTOR信号通路对脑缺血再灌注损伤认知功能的影响

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作者:Liying Yang, Yingying Zhang, Zhongrui Yan, Feng Tian

Abstract

The role and mechanism of the mTOR signaling pathway in the impaired cognitive function in cerebral ischemia-reperfusion were examined in the present study. Sprague-Dawley (SD) rats were divided into the sham operation, cerebral ischemia, cerebral ischemia-reperfusion and cerebral ischemia-reperfusion adaptive groups. A Morris water maze test was carried out in the different treatment groups at 2 weeks after surgery to detect cognitive function. After the experimental animals were sacrificed, fluorescent quantitative PCR test was used to detect the key signaling molecules in the mTOR signaling pathway in the different treatment groups, such as mTOR, p-mTOR, AKT and p-AKT gene mRNA expression. The protein expression was determined by enzyme-linked immunosorbent assay and western blotting. mTOR expression and localization in the different treatment groups was detected by immunohistochemistry, and the positive cell rate was determined. Compared with the sham operation group, the levels of mTOR, p-mTOR, AKT and p-AKT mRNAs and hippocampal proteins were significantly lower in the cerebral ischemia group and cerebral ischemia-reperfusion group (P<0.05). Levels of mTOR, p-mTOR, AKT and p-AKT mRNAs and proteins in the cerebral ischemia-reperfusion adaptive group decreased but did not show significant differences (P>0.05). The Morris water maze results showed that, the adaptive ability and the cognitive functions were improved significantly in the cerebral ischemia-reperfusion adaptive group when compared with the cerebral ischemia and cerebral ischemia-reperfusion groups (P<0.05). The number of mTOR-positive cells in hippocampus was significantly higher in the sham operation and cerebral ischemia-reperfusion adaptive groups, but there was no difference between these groups. In conclusion, mTOR signaling pathway improves the cognitive function in cerebral ischemia-reperfusion in rats.

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