Functional analysis of IFITM3 in neurodevelopmental impairments

2012 Fiscal Year Final Research Report

• Project/Area Number: 22390046
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Nagoya University
• Principal Investigator: YAMADA Kiyofumi 名古屋大学, 医学部附属病院, 教授 (30303639)
• Co-Investigator(Kenkyū-buntansha): MIZOGUCHI Hiroyuki 名古屋大学, 環境医学研究所, 助教 (70402568)
• Co-Investigator(Renkei-kenkyūsha): NAGAI Taku 名古屋大学, 医学部附属病院, 准教授 (10377426) ; HIBI Yoko 名古屋大学, 医学部附属病院, 特任助教 (70295616)
• Project Period (FY): 2010 – 2012
• Keywords: 神経発達障害 / 統合失調症 / アストログリア細胞 / 神経-グリア相互作用 / polyI:C / IFITM3 / エンドサイトーシス

Research Abstract

The role of interferon-induced transmembrane protein 3 (IFITM3) in the CNS is largely unknown, despite the fact that its expression is increased in the brains of patients with neurologic and neuropsychiatric diseases. In the present study we show the role of IFITM3 in long-lasting neuronal impairments in mice following polyI:C-induced immune challenge during the early stages of development. Our findings suggest that the induction of IFITM3 expression in astrocytes by the activation of the innate immune system during the early stages of development has non-cell autonomous effects that affect subsequent neurodevelopment, leading to neuropathological impairments and brain dysfunction, by impairing endocytosis in astrocytes.

Research Products

• [Journal Article] Animal models of schizophrenia for molecular and pharmacological intervention and potential candidate molecules (2013)
  • Author(s): Mouri A, Nagai T, Ibi D and Yamada K
  • Journal Title: Neurobiol. Dis Volume: 53 Pages: 61-74
  • DOI: DOI:10.1016/j.nbd.2012.10.025
  • Peer Reviewed
• [Journal Article] Neuronal PAS domain domain protein 4 (Npas4) regulates neurite outgrowth and phosphorylation of synapsin I. (2013)
  • Author(s): Yun J, Nagai T, Furukawa-Hibi Y, Kuroda K, Kaibuchi K, Greenberg ME, and Yamada K
  • Journal Title: J. Biol. Chem. Volume: 288 Pages: 2655-2664
  • DOI: DOI:10.1074/jbc.M112.413310.
  • Peer Reviewed
• [Journal Article] D-serine ameliorates neonatal PolyI:C treatment-induced emotional and cognitive impairments in adult mice (2012)
  • Author(s): Nagai T, Yu J, Kitahara Y, Nabeshima T and Yamada K
  • Journal Title: J. Pharmacol. Sci Volume: 120 Pages: 213-227
  • DOI: DOI:10.1254/jphs.12142FP
  • Peer Reviewed
• [Journal Article] Transcriptional suppression of the neuronal PAS domain 4 (Npas4) gene by stress via the binding of agonist-bound glucocorticoid receptor to its promoter (2012)
  • Author(s): Furukawa-Hibi Y, Yun J, Nagai T, and Yamada K
  • Journal Title: J Neurochem Volume: 123 Pages: 866-875
  • DOI: DOI:10.1111/jnc.12034
  • Peer Reviewed
• [Journal Article] Effects of antipsychotics on the behavioral deficits in human dominant-negative DISC1 transgenic mice with neonatal polyI:C treatment (2011)
  • Author(s): Nagai T, Kitahara Y, Ibi D, Nabeshima T, Sawa A and Yamada K
  • Journal Title: Behav Brain Res Volume: 225 Pages: 305-310
  • DOI: DOI:10.1016/j.bbr.2011.07.049.
  • Peer Reviewed
• [Journal Article] Astroglial IFITM3 mediates neuronal impairments following neonatal immune challenge in mice
  • Author(s): Ibi D, Nagai T, Nakajima A, Mizoguchi H, Kawase T, Tsuboi D, Kano S, Sato Y, Hayakawa M, Lange UC, Adams DJ, Surani MA, Satoh T, Sawa A, Kaibuchi K, Nabeshima T and Yamada K
  • Journal Title: Glia Volume: (in press)
  • DOI: DOI:10.1002/glia.22461
  • Peer Reviewed
• [Presentation] (2012)
  • Author(s): Yamada K, Ibi D, Nakajima A, Yamada S, Mizoguchi H, Nabeshima T and Nagai T
  • Organizer: 8thFENS Forum of Neuroscience
  • Place of Presentation: Barcelona International Convention Center
  • Year and Date: 20120714-18
• [Presentation] (2012)
  • Author(s): 山田清文
  • Organizer: 第86回日本薬理学会年会
  • Place of Presentation: 福岡 福岡国際会議場
  • Year and Date: 20120321-23
• [Presentation] (2011)
  • Author(s): Yamada K.
  • Organizer: Society of Biological Psychiatry 66thAnnual Scientific Meeting & Convention
  • Place of Presentation: San Francisco Hyatt Regency, Embarcadero Center
  • Year and Date: 20110512-14
• [Presentation] (2010)
  • Author(s): 衣斐大祐、永井拓、中島晶、鍋島俊隆、山田清文
  • Organizer: 第20回日本臨床精神神経薬理学会 第40回日本神経精神薬理学会合同年会
  • Place of Presentation: 仙台 仙台国際センター
  • Year and Date: 20100915-17
• [Remarks]
  • URL: http://www.med.nagoya-u.ac.jp/pharmacy/02/index.html