Neuroprotection against cerebral ischemic injury via microglial VNUT-mediated pathway

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K14815
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 46010:Neuroscience-general-related
• Research Institution: Chiba University
• Principal Investigator: HIRAYAMA Yuri 千葉大学, 大学院医学研究院, 助教 (30732804)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: ミクログリア / 脳梗塞 / VNUT / ATP

Outline of Final Research Achievements

ATP, which is the universal energy currency of life, is released into the extracellular space and acts as a neurotransmitter. ATP is known to be increased in response to transient brain ischemia, but whether this ATP increase is beneficial or harmful to cerebral ischemic injury is controversial, and a mechanism underlying the ATP increase is unknown. Vesicular nucleotide transporter (VNUT), a transporter responsible for vesicular storage of ATP, plays an important role in purinergic signaling in various physiological and pathological phenomena. Here, we show that the ATP exocytosis via VNUT in microglia, a type of glial cell, contributes to neuroprotection against cerebral ischemic injury.

Free Research Field

神経薬理学

Academic Significance and Societal Importance of the Research Achievements

これまでの脳虚血障害治療薬の標的は神経細胞であった。本研究により、グリア細胞（ミクログリア）はプリン作動性シグナルを介して、脳虚血障害に対して保護作用をもたらすことが明らかとなった。これにより、全く新しい脳卒中治療戦略に繋がる基礎データを蓄積することができた。