Lithium chloride ameliorated spatial cognitive impairment through activating mTOR phosphorylation and inhibiting excessive autophagy in the repeated cerebral ischemia-reperfusion mouse model

氯化锂通过激活 mTOR 磷酸化和抑制过度自噬改善小鼠反复脑缺血再灌注模型中的空间认知障碍

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作者:Yining Xiao, Mingyue Fan, Wei Jin, William A Li, Yanqiu Jia, Yanhong Dong, Xin Jiang, Jing Xu, Nan Meng, Peiyuan Lv

Abstract

Lithium has been previously demonstrated to alleviate cognitive impairment caused by neurodegenerative diseases and acute brain injuries; however, the specific mechanism remains elusive. In the present study, the C57BL/6 mouse model of spatial cognitive impairment induced by repeated cerebral ischemia-reperfusion was established. Morris water maze test was performed to evaluate the levels of spatial cognitive impairment. Nissl staining was used to observe any morphological alterations, whilst western blotting was performed to measure the expression levels of microtubule-associated protein light chain 3 (LC3) and Beclin1 in addition to mTOR phosphorylation. LiCl was found to significantly improve spatial learning and memory impairments according to data from the Morris water maze test. Nissl staining indicated that LiCl inhibited neuronal damage in the CA1 region of the hippocampus. Additionally, LiCl increased mTOR phosphorylation, reduced beclin1 expression and reduced the LC3 II/I expression ratio. Taken together, these findings suggest that LiCl may alleviate the spatial cognitive impairment induced by repeated cerebral ischemia-reperfusion. This observation may be attributed to the inhibition of excessive autophagy by LiCl through mTOR signaling activation.

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