Analysis of sodium pump knockout mice as a pathophysiological model for familial hemiplegic migraine type 2

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461284
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Hyogo Medical University
• Principal Investigator: IKEDA KEIKO 兵庫医科大学, 医学部, 教授 (10265241)
• Co-Investigator(Renkei-kenkyūsha): KAWAKAMI KIYOSHI 自治医科大学, 医学部, 教授 (10161283) ; SATAKE SHIN-ICHIRO 自然科学機構, 生理学研究所, 助教 (30360340)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: ナトリウムポンプ / α2サブユニット / 片頭痛 / 痙攣 / 皮質拡延性抑制 / 電気生理学

Outline of Final Research Achievements

The sodium pump α2 subunit is expressed in central nervous tissue, particularly astrocytes and pyramidal cells in the hippocampus. Mutations in ATP1A2 encoding the;sodium pump α2 subunit cause Familial hemiplegic migraine type 2 (FHM2), an autosomal dominant inheritance migraine with aura and motor weakness and in some cases with seizures and cerebellar symptoms. To understand pathophysiology of migraine and develop novel therapeutics and drugs, we examined the Atp1a2 knockout heterozygous mice by histological and electrophysiological analyses. We found that increased sensitivity of induction of CSD (cortical spreading depression) response in the knockout heterozygous mice compared with wild-type littermate mice. We also established the novel transgenic mouse line harboring homologous mutations found in patients. We have examined their sensitivities to seizures and behaviors, and evaluated them as migraine-model mice.

Free Research Field

神経生理学