Scrap& build of synapse towards understanding neuropsychiatric disorders

2020 Fiscal Year Final Research Report

• Project Area: Dynamic regulation of brain function by Scrap & Build system
• Project/Area Number: 16H06463
• 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: Kobe University (2019-2020); Institute of Physical and Chemical Research (2016-2018)
• Principal Investigator: Takumi Toru 神戸大学, 医学研究科, 教授 (00222092)
• Co-Investigator(Kenkyū-buntansha): 萬代 研二 北里大学, 医学部, 教授 (50322186)
• Project Period (FY): 2016-06-30 – 2021-03-31
• Keywords: シナプス / 自閉症

Outline of Final Research Achievements

Takumi found Neuroligin 1 mutation related to synapse formation from genetic analysis of autistic families. The model mouse with the point mutation was produced, and the social behavior was abnormal. An integrated analysis of 15q dup mice as an autism model mouse showed abnormalities in serotonin neurons mainly in the raphe nucleus, E/I imbalance in the somatosensory cortex. These abnormalities were improved by serotonin replacement therapy during the developmental stage. When fMRI under mouse arousal was constructed and 15q dup mice were analyzed, the neuronal functional connectivity was reduced. Our collaborator, Mandai, elucidates the mechanisms by which afadin regulates synaptic formation and synaptic transmission. αN-catenin, a membrane-lining protein of cadherin, NGL -3, an adhesion molecule, and MAGUIN, a molecule in the postsynaptic density, were involved in these mechanisms.

Free Research Field

脳科学

Academic Significance and Societal Importance of the Research Achievements

自閉症をはじめとする精神疾患の原因は、まだほとんど不明である。しかしながら、昨今のヒト遺伝学的研究の進展により、シナプスの異常との関連が示唆されており、精神疾患はいわばシナプス病と呼んでも過言ではないようになった。本研究では、自閉症におけるシナプス表現型と病態との関係を明らかにした。