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 

作者机构：Department of OrthopedicsFirst Affiliated Hospital of Nanjing Medical University Department of OrthopedicsBen Q Hospital Affiliated to Nanjing Medical University Department of OrthopedicsAffiliated Jiangning Hospital of Nanjing Medical University 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2018年第13卷第9期

页      面：1552-1560页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100204[医学-神经病学] 10[医学] 

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 

主　　题：nerve regeneration mitochondrial division inhibitor 1 neurons apoptosis mitochondria division dynamin-related protein-I phospho-dynamin-related protein-1 Bax glutamate colocalization neural regeneration 

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.