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Neuroprotective effects of fatty acid amide hydrolase catabolic enzyme inhibition in a HIV-1 Tat model of neuroAIDS
https://oist.repo.nii.ac.jp/records/872
https://oist.repo.nii.ac.jp/records/8728aa12d9b-12a4-462f-b9bf-b05311c8896b
名前 / ファイル | ライセンス | アクション |
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1-s2.0-S0028390818305082-main (4.9 MB)
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Creative Commons
Attribution-NonCommercial-NoDerivatives 4.0 International (https://creativecommons.org/licenses/by-nc-nd/4.0/) |
Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2019-05-16 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Neuroprotective effects of fatty acid amide hydrolase catabolic enzyme inhibition in a HIV-1 Tat model of neuroAIDS | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者(英) |
Hermes, Douglas J.
× Hermes, Douglas J.× Xu, Changqing× Poklis, Justin L.× Niphakis, Micah J.× Cravatt, Benjamin F.× Mackie, Ken× Lichtman, Aron H.× Ignatowska-Jankowska, Bogna M.× Fitting, Sylvia |
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書誌情報 |
en : Neuropharmacology 巻 141, p. 55-65, 発行日 2018-08-13 |
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抄録 | ||||||
内容記述タイプ | Other | |||||
内容記述 | The HIV-1 transactivator of transcription (Tat) is a neurotoxin involved in the pathogenesis of HIV-1 associated neurocognitive disorders (HAND). The neurotoxic effects of Tat are mediated directly via AMPA/NMDA receptor activity and indirectly through neuroinflammatory signaling in glia. Emerging strategies in the development of neuroprotective agents involve the modulation of the endocannabinoid system. A major endocannabinoid, anandamide (N-arachidonoylethanolamine, AEA), is metabolized by fatty acid amide hydrolase (FAAH). Here we demonstrate using a murine prefrontal cortex primary culture model that the inhibition of FAAH, using PF3845, attenuates Tat-mediated increases in intracellular calcium, neuronal death, and dendritic degeneration via cannabinoid receptors (CB1R and CB2R). Live cell imaging was used to assess Tat-mediated increases in [Ca(2+)]i, which was significantly reduced by PF3845. A time-lapse assay revealed that Tat potentiates cell death while PF3845 blocks this effect. Additionally PF3845 blocked the Tat-mediated increase in activated caspase-3 (apoptotic marker) positive neurons. Dendritic degeneration was characterized by analyzing stained dendritic processes using Imaris and Tat was found to significantly decrease the size of processes while PF3845 inhibited this effect. Incubation with CB1R and CB2R antagonists (SR141716A and AM630) revealed that PF3845-mediated calcium effects were dependent on CB1R, while reduced neuronal death and degeneration was CB2R-mediated. PF3845 application led to increased levels of AEA, suggesting the observed effects are likely a result of increased endocannabinoid signaling at CB1R/CB2R. Our findings suggest that modulation of the endogenous cannabinoid system through inhibition of FAAH may be beneficial in treatment of HAND. | |||||
出版者 | ||||||
出版者 | Elsevier Ltd. | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0028-3908 | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 1873-7064 | |||||
PubMed番号 | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | PMID | |||||
関連識別子 | info:pmid/30114402 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | info:doi/10.1016/j.neuropharm.2018.08.013 | |||||
権利 | ||||||
権利情報 | © 2018 The Author(s). | |||||
情報源 | ||||||
関連名称 | http://creativecommons.org/licenses/BY-NC-ND/4.0/ | |||||
関連サイト | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://www.sciencedirect.com/science/article/pii/S0028390818305082?via%3Dihub | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 |