Physiological role of Na-pump alpha2 subunit gene and pathophysiology of hemiplegic migrane

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08629
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Jichi Medical University
• Principal Investigator: Kawakami Kiyoshi 自治医科大学, 医学部, 教授 (10161283)
• Research Collaborator: Ikeda Keiko ; Sugimoto Hiroki ; Unekawa Miyuki ; Suzuki Norihiro
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 家族性偏頭痛 / ナトリウムポンプ / カルシウムイメージング / 大脳皮質拡延性抑制

Outline of Final Research Achievements

1. The mice habouring mutation of E700K of Atp1a2, which has been identified as causative mutation of familial hemiplegic migraine, showed fast spreading of CSD and slow recovery from the potential drop. The threshold of CSD induction was lower in the female mutant mice.
2. We analyzed the change of Ca2+ concentration of neuron and astrocyte in vivo. (1) The number of astrocytes that showed the increment of Ca2+ concentration was higher in the Atp1a2 deficient mice. (2) The synchrony of intracellular Ca2+ concentration variation was significantly lower in the astrocytes of Atp1a2 deficient mice.
3. The expression of Iba-1, which is known as a marker of inflammation was augmented in the Atp1a2 deficient mice.

Free Research Field

病態医化学

Academic Significance and Societal Importance of the Research Achievements

これらにより、ヒト患者で見つかる変異を導入したマウスが、CSDの属性に変化をきたしており、偏頭痛のモデルとして有効であることを明らかにできた。これらの結果により、Atp1a2欠損マウスのアストロサイトでの機能的な変化が示唆された。