| Project/Area Number |
25861006
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Psychiatric science
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| Research Institution | Tottori University |
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Principal Investigator |
IWATA Masaaki 鳥取大学, 医学部附属病院, 講師 (40346367)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2013: ¥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 / NLRP3 / インフラマソーム / IL-1β / IL-1beta / アストロサイト / マイクログリア / ATP / グルタミン酸 / 国際情報交換 |
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| Outline of Final Research Achievements |
The mechanisms underlying stress-induced inflammation that contribute to major depression are unknown. Here we show that stress increases extracellular ATP in the hippocampus and increases the inflammatory cytokine interleukin-1β (IL-1β) in the hippocampus via the purinergic type 2X7 receptor (P2X7R) and the innate immune complex NLRP3 inflammasome (nucleotide-binding, leucine-rich repeat, pyrin domain containing 3). We show that administration of a P2X7R antagonist completely blocks the release of IL-1β, as well as another stress-induced cytokine, tumor necrosis factor a, and the cellular and behavioral deficits caused by stress. Moreover, we show that stress activates the NLRP3 inflammasome, while NLRP3 deletion null mutant mice are resistant to developing depressive behaviors caused by chronic stress. These findings indicate that the ATP-P2X7R NLRP3 inflammasome pathway provides novel therapeutic targets for the treatment of stress-related mood disorders.
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