Development of preventative measures against epilepsy using novel model animals (kick-in)

使用新型模型动物开发癫痫预防措施（启动）

• 批准号: 23659529
• 负责人: HIROSE Shinichi
• 金额: $ 2.33万
• 依托单位: Fukuoka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23659529/
• 关键词: モデル動物; フロセミド; てんかん

Dravet syndrome results from various mutations of SCN1A, the gene encoding a1 subunit of Nav1.1 channel. Microdeletion of chromosome including SCN1A leads the most severe phenotype of Dravet syndrome. We have successfully genetically engineered mice bearing a heterozygous microdeletion of Scn1a, the mouse homologue of human SCN1A. The mice exhibited severe convulsions and epileptic discharges on Electro corticogram during 4 to 8 weeks of age. We are now examining effects of NKCC1 inhibitors on the development of the phenotypes whether the inhibitors can exert a prophylactic effect. Also, we are examining the neuro-electrophysiological characteristics of the mice using the slice patch clump method on brain. Primary culture of neurons of the mice are also has been implemented.（金額単位：円）直接経費 間接経費 合 計

Drave氏综合征是由编码Nav1.1通道A1亚基的基因SCN1A的各种突变引起的。包括SCN1A在内的染色体微缺失导致Drave氏综合征最严重的表型。我们已经成功地通过基因工程使小鼠携带了人类SCN1a的小鼠同源基因Scn1a的杂合性微缺失。小鼠在4-8周龄时出现严重的惊厥和癫痫样的皮层脑电活动。我们现在正在研究NKCC1抑制剂对表型发育的影响，看看这些抑制剂是否能起到预防作用。此外，我们还使用脑切片斑块法检测了小鼠的神经电生理特征。还进行了小鼠神经元的原代培养。(金額単位:円)直接経費間接経費合計

项目成果

Update for genetics of epilepsy plenary session

癫痫遗传学全体会议更新

• 发表时间: 2011
• 作者: Shibahara I;Sonoda Y;Kanamori M;Saito R;Kumabe T;Tominaga T;Hirose S
• 通讯作者: Hirose S

Genetic analysis of Alternating Childhood

交替童年的遗传分析

• 发表时间: 2012
• 作者: Sugiura Y;Nakatsu F;Hiroyasu K;Ishii A;Hirose S;Okada M;Jibiki I;Ohno H;Kaneko S;Ugawa Y.;Ishii A,saito Y,Sasaki M,Hirose S.
• 通讯作者: Ishii A,saito Y,Sasaki M,Hirose S.

Steroid pulse therapy as an effective treatment for refractory epilepsy in children with glutamate receptor (GLUR) antibodies

类固醇脉冲疗法是治疗具有谷氨酸受体（GLUR）抗体的儿童难治性癫痫的有效方法

• 发表时间: 2011
• 作者: Yasumoto S;Ihara Y;Fujita T;Tomonoh Y;Ninomiya S;Nakamura N;Ideguchi H;Inoue T;Takahashi Y;Hirose S.
• 通讯作者: Hirose S.

Guideline for genetic diagnosis for epilepsy

癫痫基因诊断指南

• 发表时间: 2011
• 作者: 山田悠;他5名;Hirose S
• 通讯作者: Hirose S

Identification of ATP1A3 mutations by exome sequencing as the cause of alternating hemiplegia of childhood in Japanese patients.

• DOI: 10.1371/journal.pone.0056120
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Ishii A;Saito Y;Mitsui J;Ishiura H;Yoshimura J;Arai H;Yamashita S;Kimura S;Oguni H;Morishita S;Tsuji S;Sasaki M;Hirose S
• 通讯作者: Hirose S