文献类型：期刊文献

英文题名：Rapamycin Effectively Impedes Melamine-Induced Impairments of Cognition and Synaptic Plasticity in Wistar Rats

作者：Fu, Jingxuan[1,2];Wang, Hui[1,2];Gao, Jing[3];Yu, Mei[1,2];Wang, Rubin[4];Yang, Zhuo[3];Zhang, Tao[1,2]

机构：[1]Nankai Univ, Coll Life Sci, Tianjin 300071, Peoples R China;[2]Nankai Univ, Key Lab Bioact Mat, Minist Educ, Tianjin 300071, Peoples R China;[3]Nankai Univ, Sch Med, Tianjin 300071, Peoples R China;[4]East China Univ Sci & Technol, Inst Cognit Neurodynam, Shanghai 200237, Peoples R China

年份：2017

卷号：54

期号：2

起止页码：819

外文期刊名：MOLECULAR NEUROBIOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000394964100001)】；

基金：This work was supported by grants from the National Natural Science Foundation of China (11232005, 31171053), and 111 Project (B08011).

语种：英文

外文关键词：Rapamycin; Melamine; Oxidative stress; LTP; Depotentiation; Rats

摘要：Our previous investigation demonstrated that autophagy significantly reduced melamine-induced cell death in PC12 cells via inhibiting the excessive generation of ROS. In the present study, we further examine if rapamycin, used as an autophagy activator, can play a significant role in protecting neurons and alleviating the impairment of spatial cognition and hippocampal synaptic plasticity in melamine-treated rats. Male Wistar rats were divided into three groups: control, melamine-treated, and melamine-treated + rapamycin. The animal model was established by administering melamine at a dose of 300 mg/kg/day for 4 weeks. Rapamycin was intraperitoneally given at a dose of 1 mg/kg/day for 28 consecutive days. The Morris water maze test showed that spatial learning and reversal learning in melamine-treated rats were considerably damaged, whereas rapamycin significantly impeded the cognitive function impairment. Rapamycin efficiently alleviated the melamine-induced impairments of both long-term potentiation (LTP) and depotentiation, which were damaged in melamine rats. Rapamycin further increased the expression level of autophagy markers, which were significantly enhanced in melamine rats. Moreover, rapamycin noticeably decreased the reactive oxygen species level, while the superoxide dismutase activity was remarkably increased by rapamycin in melamine rats. Malondialdehyde assay exhibited that rapamycin prominently reduced the malondialdehyde (MDA) level of hippocampal neurons in melamine-treated rats. In addition, rapamycin significantly decreased the caspase-3 activity, which was elevated by melamine. Consequently, our results suggest that regulating autophagy may become a new targeted therapy to relieve the damage induced by melamine.