Understanding the schizophrenia-related neural circuits based on transposon dynamics

2022 Fiscal Year Final Research Report

• Project Area: Constructive understanding of multi-scale dynamism of neuropsychiatric disorders
• Project/Area Number: 18H05430
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kumamoto University
• Principal Investigator: Iwamoto Kazuya 熊本大学, 大学院生命科学研究部(医), 教授 (40342753)
• Project Period (FY): 2018-06-29 – 2023-03-31
• Keywords: 統合失調症 / 体細胞変異 / トランスポゾン

Outline of Final Research Achievements

In order to investigate the relationship between transposon activity and the molecular pathogenesis of psychiatric disorders, 1) we constructed reporter mice that can monitor the activity of transposable elements, and examined the dynamics of transposable elements under stress conditions related to psychiatric disorders. Specifically, we identified novel retrotransposition-enriched brain regions in the EGF-treated mouse. In addition, 2) by analyzing exome data, we established a bioinformatics pipeline for detecting novel retrotransposed genomic regions and measuring transposon expression levels from transcriptome data. 3) we performed epigenome and transcriptome analyzes in the fetal brain of maternal immune activation models.

Free Research Field

分子精神医学

Academic Significance and Societal Importance of the Research Achievements

動く（転移する）遺伝因子であるトランスポゾンは、脳内での転移により脳神経系の機能や精神神経疾患に影響を与えると考えられている。本研究では、脳内での転移の分子メカニズムの解明と精神神経疾患との関連を明らかにするため、転移現象を追跡できるレポーターマウスの作製やゲノム情報解析技術の確立を行った。また、胎仔期における様々な環境要因負荷により脳内の転移を活性化させ、影響を受ける脳領域の同定と遺伝子発現への影響などの解析を行った。