Clarifying the therapeutic mechanism of psychiatric disorders through the regulation of inflammation in the brain via microglial TRP channels
Project/Area Number |
19K20760
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Project/Area Number (Other) |
17H06940 (2017-2018)
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Research Category |
Grant-in-Aid for Research Activity Start-up
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Allocation Type | Multi-year Fund (2019) Single-year Grants (2017-2018) |
Research Field |
Psychiatric science
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Research Institution | Kyushu University |
Principal Investigator |
sato mina 九州大学, 医学研究院, 共同研究員 (90802827)
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Project Period (FY) |
2017-08-25 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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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 / 抗精神病薬 / TRPM7チャネル / TNF-α / TRPチャネル / 抗うつ薬 |
Outline of Research at the Start |
本研究では、「少なくとも一部の精神疾患患者においてはミクログリア過剰活性化が起こっており、アリピプラゾールなどの向精神薬、あるいは、フィンゴロミド(FTY720:TRPM7阻害作用あり)などによるミクログリアTRPチャネルを介したミクログリア活性化制御が治療になるのでは?」という仮説を立て、精神疾患関連モデルマウス実験とともに、精神疾患患者由来iMG細胞を用いた橋渡し研究による双方向性アプローチで仮説解明を志す。
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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.
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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。
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Report
(4 results)
Research Products
(7 results)
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[Journal Article] Development and validation of the 22-item Tarumi's modern-type depression trait scale; Avoidance of social roles, Complaint and low Self-esteem (TACS-22)2019
Author(s)
Kato TA, Katsuki R, Kubo H, Shimokawa N, Sato-Kasai M, Hayakawa K, Kuwano N, Umene-akano W, Tateno M, Setoyama D, Kang D, Watabe M, Sakamoto S, Teo AR, Kanba S
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Journal Title
Psychiatry and clinical neurosciences
Volume: in press
Issue: 8
Pages: 448-457
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Neuron-related blood inflammatory markers as an objective evaluation tool for major depressive disorder: An exploratory pilot case-control study2018
Author(s)
Kuwano N, Kato TA*, Mitsuhashi M, Sato-Kasai M, Shimokawa N, Hayakawa K, Ohgidani M, Sagata N, Kubo H, Sakurai T, Kanba S
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Journal Title
Journal of Affective Disorders
Volume: 240
Pages: 88-98
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Development and validation of the 25-item Hikikomori Questionnaire (HQ-25)2018
Author(s)
Teo AR*, Chen JI, Kubo H, Katsuki R, Sato-Kasai M, Shimokawa N, Hayakawa K, Umene-Nakano W, Aikens, JE, Kanba S, Kato TA
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Journal Title
Psychiatry and Clinical Neurosciences
Volume: 72(10)
Issue: 10
Pages: 780-788
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Tryptophan-kynurenine and lipid related metabolites as blood biomarkers for first-episode drug-naive patients with major depressive disorder: an exploratory pilot case-control study.2018
Author(s)
Kuwano N, Kato TA, Setoyama D, Sato-Kasai M, Shimokawa N, Hayakawa K, Ohgidani M, Sagata N, Kubo H, Kishimoto J, Kang D, Kanba S
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Journal Title
Journal of Affective Disorders
Volume: 231
Pages: 74-82
DOI
Related Report
Peer Reviewed
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[Journal Article] Blood biomarkers of Hikikomori, a severe social withdrawal syndrome.2018
Author(s)
Hayakawa K, Kato TA*, Watabe M, Teo AR, Horikawa H, Shimokawa N, Sato-Kasai M, Kubo H, Ohgidani M, Sagata N, Toda H, Tateno M, Shinfuku N, Kishimoto J, Kanba S
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Journal Title
Scientific Reports
Volume: 8
Issue: 1
Pages: 2884-2884
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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