Mitochondrial division inhibitor 1 protects cortical neurons from excitotoxicity:a mechanistic pathway  

作　　者：Kuai Zhou Hai-Yuan Yang Peng-Yu Tang Wei Liu Yong-Jun Luo Bin Lv Jian Yin Tao Jiang Jian Chen Wei-Hua Cai Jin Fan 

机构地区：[1]Department of Orthopedics,First Affiliated Hospital of Nanjing Medical University [2]Department of Orthopedics,Ben Q Hospital Affiliated to Nanjing Medical University [3]Department of Orthopedics,Affiliated Jiangning Hospital of Nanjing Medical University

出　　处：《Neural Regeneration Research》2018年第9期1552-1560,共9页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,No.81371967 and 81401807;a grant from the 5th Phase of "Project 333"of Jiangsu Province of China,No.BRA2016512;a grant from the Six Talent Peaks Project of Jiangsu Province of China,No.2014-WSN-012

摘　　要：Mitochondrial division inhibitor 1（Mdivi-1） is a selective cell-permeable inhibitor of dynamin-related protein-1（Drp1） and mitochondrial division.To investigate the effect of Mdivi-1 on cells treated with glutamate,cerebral cortex neurons isolated from neonatal rats were treated with 10 m M glutamate for 24 hours.Normal cultured cells and dimethyl sulfoxide-cultured cells were considered as controls.Apoptotic cells were detected by flow cytometry.Changes in mitochondrial morphology were examined by electron microscopy.Drp1,Bax,and casp ase-3 expression was evaluated by western blot assays and immunocytochemistry.Mitochondrial membrane potential was detected using the JC-1 probe.Twenty-four hours after 10 m M glutamate treatment,Drp1,Bax and caspase-3 expression was upregulated,Drp1 and Bax were translocated to mitochondria,mitochondrial membrane potential was decreased and the rate of apoptosis was increased.These effects were inhibited by treatment with 50 μM Mdivi-1 for 2 hours.This finding indicates that Mdivi-1 is a candidate neuroprotective drug that can potentially mitigate against neuronal injury caused by glutamate-induced excitotoxicity.Mitochondrial division inhibitor 1（Mdivi-1） is a selective cell-permeable inhibitor of dynamin-related protein-1（Drp1） and mitochondrial division.To investigate the effect of Mdivi-1 on cells treated with glutamate,cerebral cortex neurons isolated from neonatal rats were treated with 10 m M glutamate for 24 hours.Normal cultured cells and dimethyl sulfoxide-cultured cells were considered as controls.Apoptotic cells were detected by flow cytometry.Changes in mitochondrial morphology were examined by electron microscopy.Drp1,Bax,and casp ase-3 expression was evaluated by western blot assays and immunocytochemistry.Mitochondrial membrane potential was detected using the JC-1 probe.Twenty-four hours after 10 m M glutamate treatment,Drp1,Bax and caspase-3 expression was upregulated,Drp1 and Bax were translocated to mitochondria,mitochondrial membrane potential was decreased and the rate of apoptosis was increased.These effects were inhibited by treatment with 50 μM Mdivi-1 for 2 hours.This finding indicates that Mdivi-1 is a candidate neuroprotective drug that can potentially mitigate against neuronal injury caused by glutamate-induced excitotoxicity.

关 键 词：nerve regeneration mitochondrial division inhibitor 1 neurons apoptosis mitochondria division dynamin-related protein-I phospho-dynamin-related protein-1 Bax GLUTAMATE COLOCALIZATION neural regeneration 

分 类 号：R741[医药卫生—神经病学与精神病学]