The effect of maternal immune activation on drug addiction

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K08960
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Saitama Medical University
• Principal Investigator: Murakami Gen 埼玉医科大学, 医学部, 講師 (70613727)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 母胎免疫活性化 / ドーパミン

Outline of Final Research Achievements

Developmental disorders such as attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and schizophrenia remain a serious public health problem worldwide. However, the mechanism has not been elucidated and further understanding is important. In this study, we used maternal immune activation (MIA), which is one of the most frequently used animal models for the study of developmental disorders. MIA-treated mice were analyzed for locomotor activity, social behaviors and pre-pulse inhibition in adulthood. We found altered locomotor activity and pre-pulse inhibition but not social behaviors. We also analyzed cocaine-induced behavioral sensitization but MIA treatment did not have effects on the behavior. We also performed comprehensive analysis of gene expression in dopamine-related brain regions in MIA-treated mice. We found that various gene expressions were altered, providing a novel landmark in the pathogenesis of developmental disorders.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

本研究で薬物依存の脆弱性を決定する環境要因として着目したMHCIは、我々がはじめて薬物依存を制御する事を発見した分子である。予想と異なり母体免疫活性化による薬物依存への影響は本研究では観測できなかったが、MHCIが制御するドーパミン系は統合失調症、自閉症、注意欠陥多動性障害といった発達障害にも関係する。従って本研究で明らかにした母体免疫活性化によるMHCIの発現制御異常は、発達障害の原因因子にもなり得る。実際に胎児期の免疫活性化が発達障害へ寄与することが危惧されている。以上のことから本研究の成果は発達障害への影響を示唆し、その意義は大きい。