Roles for microglial calcium channels in neurodegenerative diseases

• Project/Area Number: 15K08172
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General physiology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: SAEGUSA Hironao 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (90261205)
• Research Collaborator: HUNTULA Soontaraporn ; WANG Xinshuang
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: Caチャネル / Cav1.2 / Cav2.2 / パーキンソン病 / MPTP / ミクログリア / 電位依存性Caチャネル / 神経変性疾患

Outline of Final Research Achievements

Voltage-dependent calcium channel (VDCC) has been thought to play important roles in excitatory cells such as neurons. However, we have recently clarified that N-type VDCC in microglia, a non-excitatory cell type, is also critically involved in development of neuropathic pain, an intractable pain caused by nerve injuries. In the present study, we have addressed a question whether the microglial VDCCs are also involved in pathophysiology of neurodegenerative diseases. By using cultured microglial cells and transgenic mice, where knock down of microglial VDCC is achieved, we have found the following results. Knocking down the microglial N-type VDCC lead to ameliorating neurological symptoms and on the other hand knocking down L-type VDCC results in exaggeration of the symptoms. Therefore, microglial VDCCs are actually involved in the pathophysiology of neurodegenerative diseases as well but the mechanism underlying is yet to be clarified.

Research Products

• [Journal Article] Involvement of phosphatidylinositol-3 kinase/Akt/mammalian target of rapamycin/peroxisome proliferator-activated receptor γ pathway for induction and maintenance of neuropathic pain (2018)
  • Author(s): Kondo Daisuke、Saegusa Hironao、Tanabe Tsutomu
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 499 Pages: 253-259
  • DOI: 10.1016/j.bbrc.2018.03.139
  • Peer Reviewed
• [Remarks] 東京医科歯科大学大学院 認知行動医学講座 細胞薬理学分野
  • URL: http://www.tmd.ac.jp/med/mphm/Yakuri.HTM
• [Remarks] 東京医科歯科大学大学院医歯学総合研究科細胞薬理学分野ホームページ
  • URL: http://www.tmd.ac.jp/med/mphm/Yakuri.HTM