論文

査読有り
2015年9月

Epileptogenesis and epileptic maturation in phosphorylation site-specific SNAP-25 mutant mice

EPILEPSY RESEARCH
  • Shigeru Watanabe
  • ,
  • Saori Yamamori
  • ,
  • Shintaro Otsuka
  • ,
  • Masanori Saito
  • ,
  • Eiji Suzuki
  • ,
  • Masakazu Kataoka
  • ,
  • Hitoshi Miyaoka
  • ,
  • Masami Takahashi

115
開始ページ
30
終了ページ
44
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.eplepsyres.2015.05.004
出版者・発行元
ELSEVIER SCIENCE BV

Snap25(S187A/S187A) mouse is a knock-in mouse with a single amino acid substitution at a protein kinase C-dependent phosphorylation site of the synaptosomal-associated protein of 25 kDa (SNAP-25), which is a target-soluble NSF attachment protein receptor (t-SNARE) protein essential for neurotransmitter release. Snap25(S187A/S187A) mice exhibit several distinct phenotypes, including reductions in dopamine and serotonin release in the brain, anxiety-like behavior, and cognitive dysfunctions. Homozygous mice show spontaneous epileptic convulsions, and about 15% of the mice die around three weeks after birth. The remaining mice survive for almost two years and exhibit spontaneous recurrent seizures throughout their lifetime. Here, we conducted long-term continuous video electroencephalogram recording of the mice and analyzed the process of epileptogenesis and epileptic maturation in detail. Spikes and slow-wave discharges (SWDs) were observed in the cerebral cortex and thalamus before epileptic convulsions began. SWDs showed several properties similar to those observed in absence seizures including (1) lack of in the hippocampus, (2) movement arrest during SWDs, and (3) inhibition by ethosuximide. Multiple generalized seizures occurred in all homozygous mice around three weeks after birth. However, seizure generation stopped within several days, and a seizure-free latent period began. Following a spike-free quiet period, the number of spikes increased gradually, and epileptic seizures reappeared. Subsequently, spontaneous seizures occurred cyclically throughout the life of the mice, and several progressive changes in seizure frequency, seizure duration, seizure cycle interval, seizure waveform, and the number and waveform of epileptic discharges during slow-wave sleep occurred with different time courses over 10 weeks. Anxiety-related behaviors appeared suddenly within three days after epileptic seizures began and were delayed markedly by oral administration of valproic acid. These results showed that Snap25(S187A/S187A) mice exhibited a variety of epilepsy-related phenomena, and thus, they will be useful for understanding the mechanisms of epileptogenesis, epileptic maturation, and the actions of antiepileptic drugs. (C) 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Web of Science ® 被引用回数 : 15

リンク情報
DOI
https://doi.org/10.1016/j.eplepsyres.2015.05.004
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000359958200004&DestApp=WOS_CPL
ID情報
  • DOI : 10.1016/j.eplepsyres.2015.05.004
  • ISSN : 0920-1211
  • eISSN : 1872-6844
  • Web of Science ID : WOS:000359958200004

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