Visualization of disrupted glutamate dynamics in the brain upon psychiatric disorders

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08543
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: The University of Tokyo
• Principal Investigator: Okubo Yohei 東京大学, 大学院医学系研究科(医学部), 講師 (40422282)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 統合失調症 / うつ / グルタミン酸 / 脳・神経 / 薬理学

Outline of Final Research Achievements

Although disruption of glutamate dynamics in the brain is atracting attention as a cause of psychiatric disorders, many points remain elusive. We thus set out to apply our unique glutamate fluorescence imaging technique for psychiatric disorders including schizophrenia and depression, and tried to clarify the disrupted glutamate dynamics and its mechanism in the brain. We for the first time found a spontaneous and spatially confined increase in glutamate concentration in the cerebral cortex. Since this glutamate dynamics was observed even under the inhibition of neuronal activity, release from glial cells, in particular astrocytes, was expected. It is expected to be a factor of non-neural factor for the disruption of glutamate dynamics in the pathological condition, and further analysis of the mechanism and elucidation of the causal relationship are awaited.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

精神疾患のメカニズムは未だ不明な点が多く、既存の治療法は社会的要請を十分に満たしていない。本研究で発見されたグルタミン酸動態を評価軸にして病態や既存薬の効果を解析することで、治療抵抗性の統合失調症やうつ病に対する新たな治療法の開発に資する知見が得られることが期待される。