Investigation of molecular mechanisms of LINE-1 regulation related to psychiatric disorders using animal models

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15520
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: Kumamoto University
• Principal Investigator: Murata Yui 熊本大学, 大学院生命科学研究部(医), 特別研究員(SPD・PD・RPD) (10802077)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: LINE-1 / レトロトランスポゾン / 統合失調症 / poly(I:C) / 母体免疫活性

Outline of Final Research Achievements

LINE-1 copy number was increased in the brain tissue of schizophrenic patients. However, the molecular mechanisms and the roles of LINE-1 retrotransposition in the brain are unknown. We used poly(I:C)-treated mouse, a commonly used animal model of psychiatric disorders, and confirmed that adult mice of this model showed behavioral abnormalities. We found that expression of of LINE mRNA was increased in prenatal brain. From RNA sequencing analysis of prenatal brain, expression of the genes related to RNA processing was increased. These data provided the possible regulatory mechanisms of brain LINE-1 overexpression in schizophrenia.

Free Research Field

分子脳科学

Academic Significance and Societal Importance of the Research Achievements

精神疾患の発症メカニズムはいまだ不明点が多く、その分子機構を解明することは急務である。また、脳におけるLINE-1転写・転移活性メカニズムやその影響についても解明されていない。LINE-1新規転移がどのように生じ、脳機能の異常に関与するのかを検証することは、精神疾患の病態を解明する一助になると考えられる。胎生期の免疫活性ストレスによるLINE-1制御メカニズムが明らかになれば、精神神経疾患の予防・治療戦略に寄与できると期待される。