Functional analysis of the schizophrenia-associated factor DBZ in oligodendrocytes

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K18381
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Kindai University
• Principal Investigator: SHIMIZU Shoko 近畿大学, 東洋医学研究所, 助教 (50572731)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: オリゴデンドロサイト / 統合失調症 / DISC1 / DBZ / ミエリン

Outline of Final Research Achievements

Recent studies have implicated oligodendrocyte (OL) abnormalities in schizophrenia. To better elucidate the molecular mechanisms underlying the pathophysiology of schizophrenia, we investigated the function of DISC1-Binding Zinc finger protein (DBZ) in OL differentiation as DISC1 is a risk gene of schizophrenia. We examined the dynein cofactor, nuclear distribution E homolog 1 (NDE1), which binds to DBZ in OLs. Postnatally, when myelin formation is active, NDE1 mRNA is expressed in OL lineage cells in the mouse corpus callosum. An in vitro analysis revealed that NDE1 knockdown impaired OL differentiation. In addition, overexpression of the dynein-binding region of NDE1 resulted in impairments in OL differentiation like those observed following NDE1 knockdown. These results suggested that the DBZ-NDE1-dynein complex regulates OL differentiation.

Free Research Field

神経科学