Real-time imaging of the mechanism underlying neuroinflammation-induced neuropsychiatric disorders

• Project/Area Number: 26670121
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• 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(Renkei-kenkyūsha): ITOH Norimichi 名古屋大学, 医学部附属病院, 特任助教 (30726310)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ＩＦＩＴＭ３ / アストロサイト / ＲａｂＧＤＩ / Ｆｓｔｌ１ / 神経発達障害 / 神経科学 / 脳神経疾患 / IFITM3 / RabGDI

Outline of Final Research Achievements

We have demonstrated that interferon-induced transmembrane protein 3 (IFITM3) in astrocytes plays a crucial role in neurodevelopmental impairment in polyIC-treated mouse model of perinatal neuroinflammation. In this study, RabGDI was identified as a novel binding protein of IFITM3. Furthermore, we observed that overexpression of IFITM3 in COS7 cells resulted in an increase in the size of intracellular vesicles, probably due to an increase in Rab5 activity through the interaction with RabDGI. These findings suggest that IFITM3 facilitates the formation of multi-vesicular body (MVB), by regulating Rab5 activity through the interaction with RabGDI.

Research Products

• [Journal Article] Prenatal Nicotine Exposure Impairs the Proliferation of Neuronal Progenitors, Leading to Fewer Glutamatergic Neurons in the Medial Prefrontal Cortex. (2016)
  • Author(s): Aoyama Y, Toriumi K, Mouri A, Hattori T, Ueda E, Shimato A, Sakakibara N, Soh Y, Mamiya T, Nagai T, Kim HC, Hiramatsu M, Nabeshima T, Yamada K.
  • Journal Title: Neuropsychopharmacology Volume: 41(2) Issue: 2 Pages: 578-89
  • DOI: 10.1038/npp.2015.186
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Molecular mechanism linking BDNF/TrkB signaling with the NMDA receptor in memory: The role of Girdin in the CNS. (2016)
  • Author(s): Itoh N, Enomoto A, Nagai T, Takahashi M, Yamada K
  • Journal Title: Rev Neurosci Volume: - Issue: 5 Pages: 481-490
  • DOI: 10.1515/revneuro-2015-0072
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Nobiletin, a citrus flavonoid, improves cognitive impairment and reduces soluble Aβ levels in a triple transgenic mouse model of Alzheimer's disease (3XTg-AD). (2015)
  • Author(s): Nakajima, A., Aoyama, Y., Shin, E.J. Nam, Y., Kim, H.C. Nagai, T., Yokosuka, A., Mimaki, Y., Yokoi, T., Ohizumi, Y., Yamada, K.
  • Journal Title: Behav. Brain Res. Volume: 289 Pages: 69-77
  • DOI: 10.1016/j.bbr.2015.04.028
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Therapeutic targets for neurodevelopmental disorders emerging from animal models with perinatal immune activation. (2015)
  • Author(s): Ibi D and Yamada K
  • Journal Title: Int J Mol Sci Volume: 16 Issue: 12 Pages: 1-12
  • DOI: 10.3390/ijms161226092
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Alterations of GABAergic and dopaminergic system in mutant mice with disruption of exons 2 and 3 of the Disc1 gene. (2014)
  • Author(s): Nakai T, Nagai T, Wang R, Yamada S, Kuroda K, Kaibuchi K, Yamada K
  • Journal Title: Neurochem. Int. Volume: 74 Pages: 74-83
  • DOI: 10.1016/j.neuint.2014.06.009
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Induction of interferone-induced transmembrane protein 3 gene expression by lipopolysaccharide in astrocytes. (2014)
  • Author(s): Nakajima A, Ibi D, Nagai T, Yamada S, Nabeshima T, Yamada K
  • Journal Title: Eur. J. Pharmacol. Volume: 745 Pages: 166-175
  • DOI: 10.1016/j.ejphar.2014.08.034
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Girdin phosphorylation is crucial for synaptic plasticity and memory: A potential role in the interaction of BDNF/TrkB/Akt signaling with NMDA receptor (2014)
  • Author(s): Tsuyoshi Nakai, Taku Nagai, Motoki Tanaka, Norimichi Itoh, Naoya Asai, Atsushi Enomoto, Masato Asai, Shinnnosuke Yamada, Ali Bin Saifullah, Masahiro Sokabe, Masahide Takahashi, Kiyofumi Yamada
  • Journal Title: The Journal of Neuroscience Volume: 34 Issue: 45 Pages: 14995-15008
  • DOI: 10.1523/jneurosci.2228-14.2014
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] IFITM3による細胞内輸送系の制御機構 (2016)
  • Author(s): 伊藤教道、永井拓、中島晶、衣斐大祐、山田清文
  • Organizer: 第89回日本薬理学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-03-09
• [Presentation] リン酸化GirdinはNMDA受容体を介して神経可塑性を制御する (2014)
  • Author(s): 永井拓、中井剛、田中基樹、浅井直也、榎本篤、曽我部正博、高橋雅英、山田清文
  • Organizer: 第24回日本臨床精神神経薬理学会・第44回日本神経精神薬理学会
  • Place of Presentation: 愛知県名古屋市 名古屋国際会議場
  • Year and Date: 2014-11-20 – 2014-11-22
• [Presentation] マトリックスメタロプロテアーゼはpolyI:C誘発性自然免疫活性化により惹起される神経発達障害を仲介する (2014)
  • Author(s): 永井拓、山田真之亮、山田清文
  • Organizer: 第8回次世代を担う若手医療薬科学シンポジウム
  • Place of Presentation: 熊本県熊本市 熊本大学
  • Year and Date: 2014-11-15 – 2014-11-16
• [Presentation] IQGAP1の神経細胞における機能解折 (2014)
  • Author(s): 伊藤教道、渡辺崇、永井拓、貝淵弘三、山田清文
  • Organizer: 第126回日本薬理学会近畿部会
  • Place of Presentation: 和歌山県和歌山市 和歌山県ＪＡビル
  • Year and Date: 2014-10-24
• [Presentation] Matrix metalloproteinase-3とpolyI:C誘発性自然免疫活性化により惹起される神経発達障害 (2014)
  • Author(s): 永井拓、山田真之亮、山田清文
  • Organizer: 第37回日本神経科学大会
  • Place of Presentation: 神奈川県横浜市 パシフィコ横浜
  • Year and Date: 2014-09-11 – 2014-09-13
• [Remarks] 名古屋大学大学院医学系研究科 医療薬学・医学部附属病院薬剤部
  • URL: http://www.med.nagoya-u.ac.jp/pharmacy/