Molecular mechanism underlying neurodevelopmental impairment induced by perinatal viral infection

• Project/Area Number: 16K21080
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry; Embryonic/Neonatal medicine
• Research Institution: Nagoya University
• Principal Investigator: ITOH Norimichi 名古屋大学, 医学部附属病院, 特任助教 (30726310)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: IFITM3 / astrocyte / polyI:C / 周産期ウイルス感染 / RabGDI / Rab5 / 神経科学 / シグナル伝達

Outline of Final Research Achievements

Viral infection in perinatal period increases the risk of psychiatric disorders in the offspring. Polyinosinic-polycytidylic acid (polyI:C) induces strong immune reaction which mimic viral infection. Previous findings showed that interferon-induced transmembrane protein 3 (IFITM3) is a key molecule in polyI:C-induced neuronal impairment. It is unknown how IFITM3 mediates polyI:C-induced neuronal impairment. The purpose of this study is to understand the role of IFITM3 in polyI:C-dependent neuronal impairment. We identified Rab GTPase dissociation inhibitor as novel IFITM3-interacting protein by proteomic analysis. IFITM3 was colocalized with RabGDI in cultured astrocytes. We found that expression of IFITM3 increased the EEA1-poisitive vesicle size. We also found that forced expression of dominant negative Rab5 in astrocytes partially ameliorated polyI:C-indecd neuronal impairment. These results suggest that IFITM3 may mediate polyI:C-induced neruonal impairment through RabGDI.

Research Products

• [Journal Article] Repetitive and compulsive-like behaviors lead to cognitive dysfunction in Disc1Δ2-3/Δ2-3 mice (2018)
  • Author(s): Wulaer B, Nagai T, Sobue A, Itoh N, Kuroda K, Kaibuchi K, Nabeshima T, Yamada K
  • Journal Title: Genes Brain Behav Volume: 印刷中 Issue: 8
  • DOI: 10.1111/gbb.12478
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Astroglial major histocompatibility complex class I following immune activation leads to behavioral and neuropathological changes. (2018)
  • Author(s): A Sobue, N Ito, T Nagai, W Shan, K Hada, Nakajima A, Y Murakami, A Mouri, Y Yamamoto, T Nabeshima, K Saito, K Yamada
  • Journal Title: Glia Volume: 66 Issue: 5 Pages: 1034-52
  • DOI: 10.1002/glia.23299
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Neuronal PAS domain protein 4 (Npas4) controls neuronal homeostasis in pentylenetetrazole-induced epilepsy through the induction of Homer1a. (2017)
  • Author(s): 2.Shan W, Nagai T, Tanaka M, Itoh N, Furukawa-Hibi Y, Nabeshima T, Sokabe M, Yamada K.
  • Journal Title: J Neurochem. Volume: - Issue: 1 Pages: 19-33
  • DOI: 10.1111/jnc.14274
  • Peer Reviewed / Open Access
• [Journal Article] Valocin-containing protein (VCP) is a novel IQ motif containing GTPase activating protein 1 (IQGAP1) interacting protein. (2017)
  • Author(s): Itoh, N., Nagai, T,, Watanabe, T., Taki, K., Nabeshima, N., Kaibuchi, K., Yamada, K.
  • Journal Title: Biochem Biophys Res Commun. Volume: 493 Issue: 4 Pages: 1384-1389
  • DOI: 10.1016/j.bbrc.2017.09.159
  • Peer Reviewed / Open Access
• [Presentation] アストロサイトに由来するMHC classIの機能解析 (2018)
  • Author(s): 伊藤 教道、祖父江 顕、永井 拓、シャン ウェイ、中島 晶、村上 ゆき、毛利 彰宏、山本 やすこ、鍋島 俊隆、斎藤 邦明、山田 清文
  • Organizer: 第１３８回日本薬理学会関東部会
• [Presentation] IFITM3 regulates polyI:C-induced neuronal impairment via Rab small GTPase (2017)
  • Author(s): Norimichi Itoh, Taku Nagai, Daisuke Ibi, Akira Nakajima, Toshitaka Nabeshima, Kiyofumi Yamada
  • Organizer: SfN2017
  • Int'l Joint Research
• [Presentation] Up-regulation of astrocyte-derived immune-related genes contributes to behavioral impairment. (2017)
  • Author(s): Norimichi Itoh, Taku Nagai, Akira Sobue, Daisuke Ibi, Akira Nakajima, Toshitaka Nabeshima, Kiyofumi Yamada
  • Organizer: IBNS2017
  • Int'l Joint Research
• [Presentation] IFITM3による細胞内輸送の制御機構 (2016)
  • Author(s): 伊藤教道、永井拓、衣斐大祐、中島晶、鍋島俊隆、山田清文
  • Organizer: 第18回応用薬理シンポジウム
  • Place of Presentation: 名古屋大学 医学部 医系研究棟1号館 地下会議室（愛知県名古屋市）
  • Year and Date: 2016-08-05