title: Dynamin-Related Protein 1 Promotes Mitochondrial Fission and Contributes to The Hippocampal Neuronal Cell Death Following Experimental Status Epilepticus.
abstract: Prolonged seizure activity may result in mitochondrial dysfunction and lead to cell death in the hippocampus. Mitochondrial fission may occur in an early stage of neuronal cell death. This study examined the role of the mitochondrial fission protein dynamin-related protein 1 (Drp1) in the hippocampus following status epilepticus.
  
  
  
  Kainic acid (KA) was microinjected unilaterally into the hippocampal CA3 area in Sprague Dawley rats to induce prolonged seizure activity. Biochemical analysis, electron microscopy, and immunofluorescence staining were performed to evaluate the subsequent molecular and cellular events. The effects of pretreatment with a mitochondrial fission protein inhibitor, Mdivi-1 (2 nmol), were also evaluated.
  
  
  
  Phosphorylation of Drp1 at serine 616 (p-Drp1(Ser616)) was elevated from 1 to 24 h after the elicited seizure activity. Pretreatment with Mdivi-1 decreased the Drp1 phosphorylation at Ser616 and limited the mitochondrial fission. Mdivi-1 rescued the Complex I dysfunction, decreased the levels of oxidized proteins, decreased the activation of cytochrome c/caspase-3 signaling, and blunted cell death in CA3 neurons.
  
  
  
  Our findings suggest that activation of p-Drp1(Ser616) is related to seizure-induced neuronal damage. Modulation of p-Drp1(Ser616) expression is accompanied by decreases in mitochondrial fission, mitochondrial dysfunction, and oxidation, providing a neuroprotective effect against seizure-induced hippocampal neuronal damage.
authors: Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.|Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors: Shang-Der
authors: SD
authors: Chen
authors: Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors: Yen-Yi
authors: YY
authors: Zhen
authors: Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors: Jui-Wei
authors: JW
authors: Lin
authors: Department of Neurology, National Cheng Kung University Hospital, Tainan, Taiwan.
authors: Tsu-Kung
authors: TK
authors: Lin
authors: Department of Neurology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Chin-Wei
authors: CW
authors: Huang
authors: Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors: Chia-Wei
authors: CW
authors: Liou
authors: Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors: Samuel H H
authors: SH
authors: Chan
authors: Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.|Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.|Department of Neurology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Biological Science, National Sun Yat-sen University, Kaohsiung, Taiwan.
authors: Yao-Chung
authors: YC
authors: Chuang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D034281:Dynamins / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D007839:Functional Laterality; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D063154:Mitochondrial Dynamics / Q000187:drug effects*; D009243:NAD / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D052999:Quinazolinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000378:metabolism; D013226:Status Epilepticus / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control
chemical_list: C549041:3-(2,4-dichloro-5-methoxyphenyl)-2-sulfanyl-4(3H)-quinazolinone; D018690:Excitatory Amino Acid Agonists; D052999:Quinazolinones; D009243:NAD; D012694:Serine; D053148:Caspase 3; C519851:Dnm1l protein, rat; D034281:Dynamins; D010751:Phosphopyruvate Hydratase; D007608:Kainic Acid
keywords: Dynamin-related protein 1; Hippocampus; Mdivi-1; Mitochondrial fission; Neuronal cell death; Status epilepticus