The changes of astrocytic purine release and metabolisms by antidepressants

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23701
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0605:Veterinary medical science, animal science, and related fields
• Research Institution: Hokkaido University
• Principal Investigator: Eguchi Ryota 北海道大学, 獣医学研究院, 助教 (10846067)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: アストロサイト / ATP / アデノシン / 抗うつ薬 / FGF2

Outline of Final Research Achievements

Antidepressants are used for treatment of depressive disorders, although little is known about the detail mechanisms of antidepressive effect. In this study, we investigated the effects of antidepressants on the functions of astrocytes. Administration of antidepressants on mice changed the gene expression of channels and enzymes which contribute to purine release and metabolisms in brain. On the other hands, antidepressants treatment for cultured astrocytes did not change the expression and activity of purine metabolic enzymes. In addition, it was shown that FGF2 regulates purine metabolic enzymes in astrocytes via ERK pathway.
These results suggest that antidepressants may not directly affect astrocytic functions, but regulate it via cells in the central nervous system such as neurons and microglia.

Free Research Field

薬理学、獣医学

Academic Significance and Societal Importance of the Research Achievements

本研究で明らかになった、抗うつ薬のによるプリン放出チャネルや代謝酵素の遺伝子発現変化は、抗うつ薬がこれらの機能を変化させることで抗うつ作用を示す可能性を提示するものであり、新たな抗うつ薬の作用メカニズムの解明につながる可能性がある。また、抗うつ薬の作用メカニズムの解明が進むことにより、うつ病態の解明やうつ病の新たな治療法の確立につながると考えられる。