Development of a biomarker for clarifying the antemortem experiences using DNA methylation of the NR3C1 promoter region in brains from pediatric victims of physical abuse

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K15399
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Legal medicine
• Research Institution: Gunma University
• Principal Investigator: Kominato Yoshihiko 群馬大学, 大学院医学系研究科, 教授 (30205512)
• Co-Investigator(Kenkyū-buntansha): 高橋 遥一郎 群馬大学, 大学院医学系研究科, 助教 (50640538) ; 佐野 利恵 群馬大学, 大学院医学系研究科, 准教授 (70455955)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 子どもの虐待 / 神経細胞 / DNAメチル化

Outline of Final Research Achievements

Diagnostic confirmation of child abuse at autopsy is a critical task for forensic pathologists. In such cases, retrieval of information on the antemortem experiences of deceased infants is crucial. Early life stress (ELS) has been suggested to cause epigenetic changes to genes in the brain, such as the Nuclear Receptor Subfamily 3, Group C, Member 1 gene (NR3C1). Conversely, evaluation of the epigenetic status in the postmortem brain might provide clues to the antemortem ELS experience. We examined DNA methylation of the 1F promoter region of NR3C1 in the postmortem brains of eight children including four ELS cases. As a result, DNA methylation was evident in ELS cases due to severe physical abuse. Epigenetic status may have potential application as a biomarker for clarifying the antemortem experiences of deceased.

Free Research Field

法医学

Academic Significance and Societal Importance of the Research Achievements

子どもの虐待には身体的な障害の他に子どもの脳発達に悪影響を及ぼすことが明らかとなってきた。また、動物実験やヒトにおける研究から、早期の有害なライフストレスが脳の神経細胞にDNAメチル化を引き起こすことが示されてきた。我々は法医解剖事例の脳を用いて虐待と神経細胞の核受容体遺伝子プロモーターのDNAメチル化の関係を調べ、頭部外傷を伴う虐待例ではDNAメチル化の増加を明らかにした。神経細胞のDNAメチル化という後天性変化が生前の精神的ストレスのバイオマーカーになる可能性が示唆された。