Therapeutic strategy for the abnormal neuronal circuit activity associated with systemic inflammation

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K19458
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Neuroscience and related fields
• Research Institution: Kobe University
• Principal Investigator: WAKE Hiroaki 神戸大学, 医学研究科, 教授 (90455220)
• Project Period (FY): 2017-06-30 – 2019-03-31
• Keywords: ミクログリア / 血液脳関門 / 体循環系炎症

Outline of Final Research Achievements

Microglia survey brain parenchyma and respond to any disruptions. Microglia also respond to systemic disease, but how this relates to blood brain barrier (BBB) integrity is largely unknown. Here we use simultaneous in vivo imaging to demonstrate that systemic inflammation induces migration of brain resident microglia to cerebral vessels. Vessel-associated microglia initially maintain BBB integrity, associated with expression of the tight junction protein Claudin-5. Further sustained inflammation results in microglia phagocytosing astrocytic end-feet and impairing BBB function. Our results show dual microglial role for BBB and have important implications for understanding how systemic immune-activation can impact on neural circuit functions.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

この一連の研究により体循環炎症に伴う中枢神経系ミクログリアの変化およびそのBBBの透過性制御機構さらにはその分子機序を明らかにすることができた。今後これらの分子を標的にした創薬戦略をすすめていくことで、体循環系の炎症に伴う精神症状の発症機序の一端をしめすことができた。