Development of novel therapeutic strategy for mental disorders targeting NLRP3 inflammasome
Project/Area Number |
17K10273
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Psychiatric science
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Research Institution | Tottori University |
Principal Investigator |
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | うつ病 / ストレス / 炎症 / NLRP3 / βヒドロキシ酪酸 / インフラマソーム / 精神疾患 / BHB |
Outline of Final Research Achievements |
Stress affects the pathophysiology of various mental illnesses including depression. Previous studies have shown that stress can be perceived by an intracellular receptor called NLRP3, resulting in damage to the neurons through inflammation. Therefore, in this study, we developed a novel therapeutic intervention using β-hydroxybutyrate (BHB), which is known to suppress NLRP3 activation. As a result, it was clarified that BHB exerts an anti-inflammatory effect and antidepressant effect by directly acting on the brain, and that BHB oral administration shows antidepressant effect. BHB is expected to be the novel strategy for the treatment of depression.
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Academic Significance and Societal Importance of the Research Achievements |
国内におけるうつ病患者数は100万人を越えるとされ、社会経済的に大きな問題となっている。うつ病患者に対する治療の中心は抗うつ薬となるが、その薬理学的な作用機序はこの70年間変わっておらず、適切に抗うつ薬を使用したとしても約1/3の患者は改善しないと報告されている。本研究成果はこれまでの抗うつ薬とは異なり、ストレスによって引き起こされる脳内炎症を抑制するという全く新たなメカニズムに立脚したものであり、その効果が証明された意義は大きい。またBHBは生体内因性のケトン体であることから、今後身体的に負荷の少ない、自己治癒力を高めるうつ病治療法が確立されることが期待される。
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Report
(3 results)
Research Products
(14 results)
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[Presentation] Intracerebral infusion of beta-hydroxybutyrate, an endogenic NLRP3 inflammasome inhibitor, produces antidepressant like effects in a rodent model of depression.2018
Author(s)
Kajitani N, Iwata M, Yamanashi T, Tsunetomi K, Miura A, Matsuo R, Nishiguchi T, Duman RS, Kaneko K.
Organizer
Society for Neuroscience
Related Report
Int'l Joint Research
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[Presentation] Central infusion of beta-hydroxybutyrate produces antidepressant like effects in the a rodent model of depression.2017
Author(s)
Naofumi Kajitani, Masaaki Iwata, Takehiko Yamanashi, Akihiko Miura, Kyouhei Tsunetomi, Saki Fukuda, Ryoichi Matsuo, Tsuyoshi Nishiguchi, Takahira Yamauchi, Ronald S. Duman, Koichi Kaneko
Organizer
Neuroscience 2017
Related Report
Int'l Joint Research
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[Presentation] Oral administration of medium chain triglyceride produces antidepressant effects in rats via the elevation of beta-hydroxybutyrate.2017
Author(s)
Akihiko Miura, Masaaki Iwata, Takehiko Yamanashi, Naofumi Kajitani, Kyouhei Tsunetomi, Saki Fukuda, Ryoichi Matsuo, Tsuyoshi Nishiguchi, Takahira Yamauchi, Ronald S. Duman, Koichi Kaneko
Organizer
Neuroscience 2017
Related Report
Int'l Joint Research
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[Presentation] Beta-hydroxybutyrate, an endogenous NLRP3 inhibitor, ameliorates the activation of astrocyte in the rat hippocampus caused by immobilization stress.2017
Author(s)
Kyouhei Tsunetomi, Masaaki Iwata, Takehiko Yamanashi, Naofumi Kajitani, Akihiko Miura, Ryoichi Matsuo, Tsuyoshi Nishiguchi, Naho Kamiya, Saki Fukuda, Koichi Kaneko
Organizer
Neuroscience 2017
Related Report
Int'l Joint Research
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