Clarifying the therapeutic mechanism of psychiatric disorders through the regulation of inflammation in the brain via microglial TRP channels

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K20760
• Project/Area Number (Other): 17H06940 (2017-2018)
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund (2019); Single-year Grants (2017-2018)
• Research Field: Psychiatric science
• Research Institution: Kyushu University
• Principal Investigator: sato mina (笠井美那) 九州大学, 医学研究院, 共同研究員 (90802827)
• Project Period (FY): 2017-08-25 – 2021-03-31
• Keywords: ミクログリア / ＴＲＰチャネル / うつ病 / 統合失調症 / 血液由来ミクログリア様（iMG）細胞 / フィンドリモド / アリピプラゾール

Outline of Final Research Achievements

We have conducted two spices studies using iMG cells from patients with psychiatric disorders as well as model mouse experiments to elucidate the hypothesis that aripiprazole and fingolimod may regulate microglial TRP channel-mediated activation for the treatment of psychiatric disorders. To elucidate this hypothesis, we have been conducting two spices studies using iMG cells derived from patients with psychiatric disorders as well as model mouse experiments. Cuprizone-treated mice, which are known as a schizophrenia-related model, showed microglial activation in specific brain regions, and aripiprazole and fingolimod treatment suppressed the activation in specific brain regions. We evaluated the cellular activation of aripiprazole and fingolimod in iMG cells derived from patients with psychiatric disorders and found that such activation was suppressed in some patient-derived iMG cells. Validation by increasing the number of cases is warranted.

Free Research Field

精神神経科学

Academic Significance and Societal Importance of the Research Achievements

従来、精神疾患の治療ターゲットは神経シナプスであったが、本研究では神経シナプスにも影響を及ぼす脳内免疫細胞ミクログリアを介した新しい治療機序を見出そうという点で先進的な試みであり、今回のモデル動物および患者由来iMG細胞を用いて萌芽的な興味深い結果を得ており、今後のミクログリア活性化制御を介した治療薬創出が期待される。