Astrocytes in Atp1a2-deficient heterozygous mice exhibit hyperactivity after induction of cortical spreading depression

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K07373
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Jichi Medical University
• Principal Investigator: SUGIMOTO Hiroki 自治医科大学, 医学部, 助教 (70515866)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 片頭痛 / マウス / カルシウムイメージング / G-CaMP7 / 家族性片麻痺性片頭痛２型

Outline of Final Research Achievements

The ATP1A2 coding a2 subunit of Na,K-ATPase, which is predominantly located in astrocytes, is a causative gene of familial hemiplegic migraine type 2 (FHM2). FHM2 model mice (Atp1a2tmCKwk/+) are susceptible to cortical spreading depression (CSD), which is profoundly related to migraine aura and headache. However, astrocytic properties during CSD have not been examined in FHM2 model mice. Using Atp1a2tmCKwk/+ crossed with transgenic mice expressing G-CaMP7 in cortical neurons and astrocytes (Atp1a2+/-), we analyzed the changes in Ca2+concentrations during CSD. The propagation speed of Ca2+ waves and the percentages of astrocytes with elevated Ca2+concentrations in Atp1a2+/- were higher than those in wild-type mice. Increased percentages of astrocytes with elevated Ca2+ concentrations in Atp1a2+/- may contribute to FHM2 pathophysiology.

Free Research Field

遺伝学

Academic Significance and Societal Importance of the Research Achievements

Naポンプα2サブユニットの変異は、家族性片麻痺性片頭痛２型（FHM2）の原因であり、同遺伝子欠損マウスで明らかにした大脳皮質アストロサイトの活動異常は、FHM2の病態解明に大いに役立つと考えられる。さらにアストロサイトの活動異常は、２型以外のFHMでも見られており、FHMの共通基盤としてアストロサイトの活動異常が存在することを示唆する。