Authors: Jingxuan Fu Hui Wang Jing Gao Mei Yu Rubin Wang Zhuo Yang Tao Zhang
Publish Date: 2016/01/15
Volume: 54, Issue: 2, Pages: 819-832
Abstract
Our previous investigation demonstrated that autophagy significantly reduced melamineinduced 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 melaminetreated rats Male Wistar rats were divided into three groups control melaminetreated and melaminetreated + 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 melaminetreated rats were considerably damaged whereas rapamycin significantly impeded the cognitive function impairment Rapamycin efficiently alleviated the melamineinduced impairments of both longterm 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 melaminetreated rats In addition rapamycin significantly decreased the caspase3 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
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