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

• Published in: Neural regeneration research Vol. 13; no. 9; pp. 1552 - 1560
• Main Authors: Zhou, Kuai, Yang, Hai-Yuan, Tang, Peng-Yu, Liu, Wei, Luo, Yong-Jun, Lv, Bin, Yin, Jian, Jiang, Tao, Chen, Jian, Cai, Wei-Hua, Fan, Jin
• Format: Journal Article
• Language: English
• Published: India Wolters Kluwer India Pvt. Ltd 01.09.2018; Medknow Publications and Media Pvt. Ltd; Medknow Publications & Media Pvt. Ltd; Department of Orthopedics, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China%Department of Orthopedics, BenQ Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu Province, China%Department of Orthopedics, Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China; Medknow Publications & Media Pvt Ltd; Wolters Kluwer Medknow Publications
• Subjects: Adenosine triphosphate; Apoptosis; Flow cytometry; Glutamate; Health aspects; Mitochondria; Morphology; nerve regeneration; mitochondrial division inhibitor 1; neurons; apoptosis; mitochondria; division; dynamin-related protein-1; phospho-dynamin-related protein-1; Bax; glutamate; colocalization; neural regeneration; Neurological research; Neurons; Penicillin; Phosphorylation; Proteins; Spinal cord; Transmission electron microscopy; United States > US; China; division; mitochondrial division inhibitor 1; neural regeneration; phospho-dynamin-related protein-1; mitochondria; Bax; apoptosis; nerve regeneration; colocalization; dynamin-related protein-1; neurons; glutamate
• ISSN: 1673-5374; 1876-7958
• DOI: 10.4103/1673-5374.235299

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 mM 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 caspase-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 mM 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.