母の免疫活性化後の認知欠陥を示す子孫における統合失調症リスク遺伝子メチル化の発達調節

Rebecca M Woods^1,2, Harry G Potter^3,4, Hager M Kowash⁵

¹Division of Evolution, Infection and Genomics, School of Biological Sciences, Manchester Academic Health Science Centre, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, M13 9PL, UK. rebecca.woods@manchester.ac.uk.

Molecular psychiatry

|August 29, 2025

まとめ

妊娠中の母親の免疫活性化 (MIA) は胎児の脳内遺伝子を変化させ,統合失調症のリスクを高めますこれらのエピジェネティックの変化は成人期に再現し認知機能の欠陥と一致し治療の標的となる可能性があります

科学分野:

神経科学
発達生物学
精神科

背景:

妊娠中の母親の感染は,子孫の神経発達障害のリスクの増加と関連しています.
エピジェネティックメカニズム,特にDNAメチル化に関わるメカニズムは,母親の免疫活性化 (MIA) と統合失調症のリスクを関連付けています.
MIAがエピジェネティックメカニズムをどのように変化させるかについての理解は限られており,認知症状の治療目標の特定を妨げています.

研究の目的:

MIAが発達中の脳における表遺伝的メカニズムとメチル化能力に及ぼす影響を調査する.
MIAに曝された子孫における特定の表遺伝的変異と認知障害との相関を特定する.
神経発達と統合失調症のリスクに対するMIA誘発の長期的影響を探る.

主な方法:

S-アデノシルメチオニン (SAM) とS-アデノシルホモシステイン (SAH) の濃度を測定し,メチル化能力の指標であるSAM/SAH比を決定する.
DNAメチルトランスファーゼ (DNMTs) の発現と活性を分析した.
DNAメチル化 (DNAm) パターンを評価し,MIAに曝された子孫の皮質で異なるメチル化遺伝子を特定した.

主要な成果:

MIAはSAM/SAH比を増加させ,胎児皮質におけるDNMTの発現と活性を高めました.
これらのメチル化経路の変化は発達初期に一時的であったが,成人期に再現し,認知障害と相関していた.
成人した子孫は統合失調症のリスクと神経発達経路に関連した異なったメチル化遺伝子を持つ変化したDNAmパターンを示した.

結論:

妊娠中の母親の免疫活性化は子孫の脳に永続的な表遺伝的変化を引き起こします
MIAによって引き起こされるこれらの表遺伝的変化は,成人期に観察される認知障害に寄与し,統合失調症の側面を反映しています.
この研究は,MIA,表皮遺伝的不調,神経発達障害の間の重要な関連を確立し,潜在的な治療法を示しています.

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