Insight into a neuropathological mechanism of functional brain network abnormalities in offspring with maternal immune activation

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10090
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Mizuma Hiroshi 国立研究開発法人理化学研究所, 生命機能科学研究センター, 研究員 (00382200)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 母体免疫活性化 / イメージング / 脳神経発達障害

Outline of Final Research Achievements

Maternal immune activation (MIA) induced by pregnant bacterial or viral infection has been considered as one of the risk factors of autistic spectrum disorder (ASD). To investigate a brain function of MIA-affected offspring, we performed resting-state functional magnetic resonance imaging (rs-fMRI) and positron emission tomography (PET). MIA model was generated by intraperitoneal injection of polyinosinic:polycytidylic acid (20 mg/kg) in pregnant mice on gestational day 12.5. The rs-fMRI study revealed that the MIA-affected offspring with social deficit had hyper-connectivity of functional networks with over and local preferred connectivity, which were similar to those of human studies in ASD patients. PET imaging showed the MIA model had low glucometabolism in the brainstem. These results suggest that abnormal functional network connectivities associated with glucometaboic activity may be crucial in the appearance of the behavioral phenotype in the MIA model.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

本研究では、MIAにより誘発された社会性行動障害をもつ動物が生後での脳幹部における神経活動の低下および大脳皮質領域での機能的ネットワーク異常を持つことが明らかとなった。今後もより詳細な神経病理メカニズムを明らかにするための動物基礎研究を進め、自閉性スペクトラム障害や統合失調症の新たな病態予測や早期の診断・治療法の開発に寄与することを考えている。