Epigenetic mechanisms in schizophrenia by immune activation during pregnancy

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K07210
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical genome science
• Research Institution: Tohoku University
• Principal Investigator: YU ZHIQIAN 東北大学, 災害科学国際研究所, 助教 (60451639)
• Research Collaborator: TOMITA HIROAKI ; NAGASAKI MASAO ; NAKAYAMA KEIKO ; HASHIMOTO KENJI ; IWAMOTO KAZUYA ; KINOSHITA KENGO
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 統合失調症 / 遺伝子発現 / メチル化 / 環境要因

Outline of Final Research Achievements

Gender differences in susceptibility to schizophrenia have been a hotly debated research issue for decades. Epidemiological evidence has shown that female offspring exposed to maternal infection during pregnancy are significantly more susceptible to developing schizophrenia. From an analysis of the offspring of poly I:C-treated pregnant mice we show that only female offspring of poly I:C-treated dams express schizophrenia-linked behavioral changes, profound genome-wide DNA hypermethylation profiles in the prefrontal cortices and postmortem prefrontal cortices of female patients with schizophrenia.

Free Research Field

災害精神医学

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、脳発達や中枢神経系恒常性を維持するDNAメチル化機能、および環境要因によるメチル化の再編を明らかにし、統合失調症の発症メカニズムの解明に寄与する。また，マウスの雌雄差を解析することで, ヒトの男女間における脳の発達、特にDNAメチル化制御の違いを解明するための新しい戦略につながり、これらの知見により統合失調症を始めとする種々の精神疾患の発症機序の解明、および有効な治療薬の開発が進むことが期待される。