A mitochondrial division inhibitor, Mdivi-1, inhibits mitochondrial fragmentation and attenuates kainic acid-induced hippocampal cell death

BMC Neuroscience

Research Article

Hwajin Kim¹  Gu Seob Roh¹  Jong Youl Lee¹  Keon Jae Park²  Won-Ho Kim² 

[1] Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, Gyeongsang National University School of Medicine, 15, 816 Beon-gil, Jinju-daero, 660-751, Jinju, Gyeongnam, Republic of Korea;Division of Metabolic Diseases, Center for Biomedical Sciences, Korea National Institute of Health, Osong, Republic of Korea;

关键词: Drp1;    Mitochondrial fission;    Neuroinflammation;    Neuronal cell death;   

DOI  :  10.1186/s12868-016-0270-y

 received in 2015-12-15, accepted in 2016-06-03,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundKainic acid (KA)-induced excitotoxicity promotes cytoplasmic calcium accumulation, oxidative stress, and apoptotic signaling, leading to hippocampal neuronal death. Mitochondria play a critical role in neuroinflammation and the oxidative stress response. Mitochondrial morphology is disrupted during KA-induced seizures; however, it is not clear whether mitochondrial fission or fusion factors are involved in KA-induced neuronal death.ResultsWe investigated the effect of Mdivi-1, a chemical inhibitor of the mitochondrial fission protein Drp1, on mitochondrial morphology and function in KA-injected mice. Mdivi-1 pretreatment significantly reduced seizure activity and increased survival rates of KA-treated mice. Mdivi-1 was protective against mitochondrial morphological disruption, and it reduced levels of phosphorylated Drp1 (Ser616) and Parkin recruitment to mitochondria. By contrast, levels of mitochondrial fusion factors did not change. Mdivi-1 also reduced KA-induced neuroinflammation and glial activation.ConclusionsWe conclude that inhibition of mitochondrial fission attenuates Parkin-mediated mitochondrial degradation and protects from KA-induced hippocampal neuronal cell death.

【 授权许可】

CC BY   
© The Author(s) 2016