Molecular mechanism underlying neurodevelopmental impairment induced by perinatal viral infection

2017 Fiscal Year Final Research Report

• 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
• Keywords: IFITM3 / astrocyte / polyI:C / 周産期ウイルス感染

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.

Free Research Field

神経化学