Dynamin-Related Protein 1 Promotes Mitochondrial Fission and Contributes to The Hippocampal Neuronal Cell Death Following Experimental Status Epilepticus

Shang Der Chen, Yen Yi Zhen, Jui Wei Lin, Tsu Kung Lin, Chin Wei Huang, Chia Wei Liou, Samuel H.H. Chan, Yao Chung Chuang

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Aims: 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. Methods: 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. Results: 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)988-999
Number of pages12
JournalCNS Neuroscience and Therapeutics
Volume22
Issue number12
DOIs
Publication statusPublished - 2016 Dec 1

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health
  • Physiology (medical)
  • Pharmacology (medical)

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