Microglial contribution on higher order of brain function and their pathology

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02598
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 48020:Physiology-related
• Research Institution: Nagoya University (2020); Kobe University (2018-2019)
• Principal Investigator: WAKE Hiroaki 名古屋大学, 医学系研究科, 教授 (90455220)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: ミクログリア / 血液脳関門 / シナプス

Outline of Final Research Achievements

In this study, we focused on microglia and aimed to elucidate psychiatric pathology from their physiological functions on synapses and blood vessels. Using in vivo imaging, we found that microglia migrate into cerebral blood vessels during systemic inflammation and contribute to the permeability of the blood-brain barrier in a time-specific manner by altering the expression of tight junction-related factors and phagocytic factors. In addition, we found that microglia modulate their synaptic effects by regulating their projection dynamics during higher brain functions (motor learning). These synaptic modulation mechanisms are dependent on the sensory input in the sensory cortex, suggesting a role for microglia in heterogeneous sensory plasticity.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

本研究成果によって、ミクログリアを標的とした中枢神経系疾患に対する新たな創薬の可能性を創出することができた。さらにミクログリアによるシナプス可塑性を制御することで、中枢神経系疾患の回復期に介入する可能性も考えられる。さらに異種感覚の可塑性のミクログリアによる制御の解明は学術的にも非常に意義深い。