Mechanism of brain function and pathogenesis induced by glial cell-mediated synaptic refinement

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06457
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 46010:Neuroscience-general-related
• Research Institution: Tohoku University
• Principal Investigator: Morizawa Yosuke 東北大学, 生命科学研究科, JSPS特別研究員(PD) (50772167)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 貪食 / グリア / アストロサイト / ミクログリア / 神経回路再編 / シナプスリモデリング / シナプス除去

Outline of Final Research Achievements

Neural circuits (synapses) remodeling is the fundamental process of learning and memory in the normal brain. In pathological conditions, it could promote the formation of inappropriate neural circuits and cause pathological deficits. In this study, we aimed to elucidate the mechanism of synapse loss.
One possible mechanism is removal of synapses by surrounding glia through phagocytosis. However, the phagocytosed materials are rapidly digested, making them difficult to detect. To solve this problem, we generated new transgenic mice line that express fluorescent probes, which are relatively resistant to mammalian lysosomes, in a cell type- and timing-specific manner. By expressing these probes on target neurons, we established a new tool that can qualitatively and quantitatively evaluate the phagocytosis of surrounding glial cells during development, learning, and brain injury.

Free Research Field

神経化学

Academic Significance and Societal Importance of the Research Achievements

貪食を可視化する新規遺伝子改変マウスの作出およびその有用性について詳細に解析・評価を行い、従来、貪食性細胞として注目されていなかった細胞による神経回路再編が、発達後の脳内でも盛んに生じていることを明らかにした。コミュニティ内で渇望されてきた新ツールの開発・提供により、他疾患モデル等におけるシナプス貪食の探索型の研究が可能となるだけでなく、神経回路再編以外にも様々な貪食研究に応用可能な有益なツールと考えられる。