BMC Neuroscience | |
A mitochondrial division inhibitor, Mdivi-1, inhibits mitochondrial fragmentation and attenuates kainic acid-induced hippocampal cell death | |
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
【 预 览 】
Files | Size | Format | View |
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RO202311094591336ZK.pdf | 3545KB | download |
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