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アイテム
Gene therapy for neuropathic pain by silencing of TNF-α expression with lentiviral vectors targeting the dorsal root ganglion in mice.
http://hdl.handle.net/10422/7701
http://hdl.handle.net/10422/7701ada5aa4c-ec73-4ff0-8a19-2202104bc3db
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
journal.pone.0092073.pdf (1.6 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||
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| 公開日 | 2014-11-07 | |||||||
| タイトル | ||||||||
| タイトル | Gene therapy for neuropathic pain by silencing of TNF-α expression with lentiviral vectors targeting the dorsal root ganglion in mice. | |||||||
| 言語 | en | |||||||
| 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_db06 | |||||||
| 資源タイプ | doctoral thesis | |||||||
| アクセス権 | ||||||||
| アクセス権 | open access | |||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||
| 著者 |
OGAWA, Nobuhiro
× OGAWA, Nobuhiro
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| 抄録 | ||||||||
| 内容記述タイプ | Abstract | |||||||
| 内容記述 | Neuropathic pain can be a debilitating condition. Many types of drugs that have been used to treat neuropathic pain have only limited efficacy. Recent studies indicate that pro-inflammatory mediators including tumor necrosis factor α (TNF-α) are involved in the pathogenesis of neuropathic pain. In the present study, we engineered a gene therapy strategy to relieve neuropathic pain by silencing TNF-α expression in the dorsal root ganglion (DRG) using lentiviral vectors expressing TNF short hairpin RNA1-4 (LV-TNF-shRNA1-4) in mice. First, based on its efficacy in silencing TNF-α in vitro, we selected shRNA3 to construct LV-TNF-shRNA3 for in vivo study. We used L5 spinal nerve transection (SNT) mice as a neuropathic pain model. These animals were found to display up-regulated mRNA expression of activating transcription factor 3 (ATF3) and neuropeptide Y (NPY), injury markers, and interleukin (IL)-6, an inflammatory cytokine in the ipsilateral L5 DRG. Injection of LV-TNF-shRNA3 onto the proximal transected site suppressed significantly the mRNA levels of ATF3, NPY and IL-6, reduced mechanical allodynia and neuronal cell death of DRG neurons. These results suggest that lentiviral-mediated silencing of TNF-α in DRG relieves neuropathic pain and reduces neuronal cell death, and may constitute a novel therapeutic option for neuropathic pain. | |||||||
| 言語 | en | |||||||
| 学位名 | ||||||||
| 言語 | ja | |||||||
| 学位名 | 博士（医学） | |||||||
| 学位授与機関 | ||||||||
| 学位授与機関識別子Scheme | kakenhi | |||||||
| 学位授与機関識別子 | 14202 | |||||||
| 言語 | ja | |||||||
| 学位授与機関名 | 滋賀医科大学 | |||||||
| 学位授与年度 | ||||||||
| 内容記述タイプ | Other | |||||||
| 内容記述 | 平成26年度 | |||||||
| 言語 | ja | |||||||
| 学位授与年月日 | ||||||||
| 学位授与年月日 | 2014-09-10 | |||||||
| 学位授与番号 | ||||||||
| 学位授与番号 | 甲第717号 | |||||||
| 書誌情報 |
en : PLoS One 巻 9, 号 3, p. e92073, 発行日 2014-03-18 |
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| 出版者 | ||||||||
| 出版者 | PLoS One | |||||||
| 言語 | en | |||||||
| 著者版フラグ | ||||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||
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| 収録物識別子タイプ | PISSN | |||||||
| 収録物識別子 | 1932-6203 | |||||||
| PMID | ||||||||
| 識別子タイプ | PMID | |||||||
| 関連識別子 | 24642694 | |||||||
| DOI | ||||||||
| 識別子タイプ | DOI | |||||||
| 関連識別子 | https://doi.org/10.1371/journal.pone.0092073 | |||||||
| 関連名称 | 10.1371/journal.pone.0092073 | |||||||
| 資源タイプ | ||||||||
| 内容記述タイプ | Other | |||||||
| 内容記述 | Thesis or Dissertation | |||||||
