Investigating the mechanisms of stress-induced depression via neuroinflammation and development of the new strategy for the treatment of depression.
Project/Area Number |
15K19729
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Psychiatric science
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Research Institution | Tottori University |
Principal Investigator |
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Project Period (FY) |
2015-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Keywords | うつ病 / ストレス / 炎症 / サイトカイン / NLRP3 / IL-1β / TNFα / インフラマソーム / NLRP3 / 炎症性サイトカイン / βヒドロキシ酪酸 |
Outline of Final Research Achievements |
We revealed that i) stress, which plays a critical role in the onset of depression, causes neuroinflammation via the innate immune system in the brain, and that ii) the key molecule which senses stress is a cytosolic pattern recognition receptor called NLRP3. We also demonstrated that beta-hydroxybutyrate (BHB), an endogenic NLRP3 inflammasome inhibitor, showed the antidepressant effects in a rodent model of chronic unpredictable stress, and that BHB attenuated the increased levels of IL-1β in the hippocampus by stress. These findings demonstrate that BHB exerts antidepressant-like effects, possibly by inhibiting NLRP3-induced neuro-inflammation in the hippocampus, and that BHB may be a novel therapeutic candidate for the treatment of stress-related mood disorders.
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Report
(3 results)
Research Products
(11 results)
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[Journal Article] Psychological Stress Activates the Inflammasome via Release of Adenosine Triphosphate and Stimulation of the Purinergic Type 2X7 Receptor.2015
Author(s)
Iwata M, Ota KT, Li XY, Sakaue F, Li N, Dutheil S, Banasr M, Duric V, Yamanashi T, Kaneko K, Rasmussen K, Glasebrook A, Koester A, Song D, Jones KA, Zorn S, Smagin G, Duman RS.
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Journal Title
Biol Psychiatry
Volume: 未定
Issue: 1
Pages: 12-22
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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