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2020 Fiscal Year Final Research Report

Elucidation of the pathophysiology related to neuro-glial networks in psychiatric disorders: Toward a pathogenesis-based diagnostic system

Research Project

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Project/Area Number 18H04040
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 52:General internal medicine and related fields
Research InstitutionNagoya University

Principal Investigator

Ozaki Norio  名古屋大学, 医学系研究科, 教授 (40281480)

Project Period (FY) 2018-04-01 – 2021-03-31
Keywordsグリア細胞 / 精神障害 / iPS細胞 / モデルマウス / 22q11.2欠失 / ASTN2
Outline of Final Research Achievements

In our genomic analysis, we found that rare genomic copy number variations (CNVs) in the glial-related gene ASTN2 are associated with the risk of psychiatric disorders (e.g., bipolar disorder). In gene expression analysis of neurospheres derived from iPS cells with ASTN2 deletion, we also found a marked decrease in expression of the ZNF558, which is suggested to be involved in the pathogenesis of psychiatric disorders. For the 22q11.2 deletion, which is associated with the risk of schizophrenia and glial abnormalities, we revealed a decrease in PERK signaling in midbrain neurons using a mouse model. Furthermore, analysis of brain tissue from schizophrenia patients identified pathological findings suggestive of myelin-oligodendrocyte abnormalities.

Free Research Field

精神医学分野

Academic Significance and Societal Importance of the Research Achievements

本研究から、グリアに関連する遺伝子が精神障害のリスクに関与することが明らかになった。またモデル生物を用いたゲノム変異の解析から、精神疾患の病態に関与する遺伝子の発現低下や神経発達に必須の細胞内シグナル伝達の低下を明らかにした。統合失調症患者脳組織の解析からもオリゴデンドロサイトと呼ばれるグリア細胞の異常を見出した。以上の知見は、精神障害病態におけるグリア異常の関与を支持するとともに、将来的には、病態に基づいた診断体系の構築や治療法の開発に資することが期待される。

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Published: 2022-01-27  

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