アマノ　ケンジ   Amano   天野　賢治    所属   東邦大学  医学部 医学科（大森病院）    職種   胚培養士
論文種別	原著
言語種別	英語
査読の有無	査読なし
表題	Impaired cortico-striatal excitatory transmission triggers epilepsy.
掲載誌名	正式名：Nature communications
掲載区分	国外
巻・号・頁	10(1),pp.1917-1917
著者・共著者	Hiroyuki Miyamoto,Tetsuya Tatsukawa,Atsushi Shimohata,Tetsushi Yamagata,Toshimitsu Suzuki,Kenji Amano,Emi Mazaki,Matthieu Raveau,Ikuo Ogiwara,Atsuko Oba-Asaka,Takao K Hensch,Shigeyoshi Itohara,Kenji Sakimura,Kenta Kobayashi,Kazuto Kobayashi,Kazuhiro Yamakawa
発行年月	2019/04/23
概要	STXBP1 and SCN2A gene mutations are observed in patients with epilepsies, although the circuit basis remains elusive. Here, we show that mice with haplodeficiency for these genes exhibit absence seizures with spike-and-wave discharges (SWDs) initiated by reduced cortical excitatory transmission into the striatum. Mice deficient for Stxbp1 or Scn2a in cortico-striatal but not cortico-thalamic neurons reproduce SWDs. In Stxbp1 haplodeficient mice, there is a reduction in excitatory transmission from the neocortex to striatal fast-spiking interneurons (FSIs). FSI activity transiently decreases at SWD onset, and pharmacological potentiation of AMPA receptors in the striatum but not in the thalamus suppresses SWDs. Furthermore, in wild-type mice, pharmacological inhibition of cortico-striatal FSI excitatory transmission triggers absence and convulsive seizures in a dose-dependent manner. These findings suggest that impaired cortico-striatal excitatory transmission is a plausible mechanism that triggers epilepsy in Stxbp1 and Scn2a haplodeficient mice.
DOI	10.1038/s41467-019-09954-9
PMID	31015467