Author:
Luo Zhong,Wang Jing,Tang Shirong,Zheng Yongsu,Zhou Xuejiao,Tian Fei,Xu Zucai
Abstract
Abstract
Background
Dynamic-related protein 1 (Drp1) is a key protein involved in the regulation of mitochondrial fission, and it could affect the dynamic balance of mitochondria and appears to be protective against neuronal injury in epileptic seizures. Equilibrative nucleoside transporter 1 (ENT1) is expressed and functional in the mitochondrial membrane that equilibrates adenosine concentration across membranes. Whether Drp1 participates in the pathogenesis of epileptic seizures via regulating function of ENT1 remains unclear.
Methods
In the present study, we used pilocarpine to induce status epilepticus (SE) in rats, and we used mitochondrial division inhibitor 1 (Mdivi-1), a selective inhibitor to Drp1, to suppress mitochondrial fission in pilocarpine-induced SE model. Mdivi-1administered by intraperitoneal injection before SE induction, and the latency to firstepileptic seizure and the number of epileptic seizures was thereafter observed. The distribution of Drp1 was detected by immunofluorescence, and the expression patterns of Drp1 and ENT1 were detected by Western blot. Furthermore, the mitochondrial ultrastructure of neurons in the hippocampal CA1 region was observed by transmission electron microscopy.
Results
We found that Drp1 was expressed mainly in neurons and Drp1 expression was significantly upregulated in the hippocampal and temporal neocortex tissues at 6 h and 24 h after induction of SE. Mitochondrial fission inhibitor 1 attenuated epileptic seizures after induction of SE, reduced mitochondrial damage and ENT1 expression.
Conclusions
These data indicate that Drp1 is upregulated in hippocampus and temporal neocortex after pilocarpine-induced SE and the inhibition of Drp1 may lead to potential therapeutic target for SE by regulating ENT1 after pilocarpine-induced SE.
Funder
the National Natural Science Foundation of China
the Guizhou Province Science and Technology Cooperation Project
the Guizhou Province Health and Family Planning Commission Science and Technology Foundation
the Zunyi City Science and Technology Foundation
Publisher
Springer Science and Business Media LLC
Subject
Neurology (clinical),General Medicine
Cited by
7 articles.
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