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Therapeutic effects of KCC2 chloride transporter activation on detrusor overactivity in mice with spinal cord injury
http://hdl.handle.net/10271/0002000113
http://hdl.handle.net/10271/000200011360ffc837-39c4-4baa-a3f0-4cbf0c13d70d
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
DT_948ronbun.pdf (1.2 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||||
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| 公開日 | 2024-03-15 | |||||||||||
| タイトル | ||||||||||||
| タイトル | Therapeutic effects of KCC2 chloride transporter activation on detrusor overactivity in mice with spinal cord injury | |||||||||||
| 言語 | en | |||||||||||
| 言語 | ||||||||||||
| 言語 | eng | |||||||||||
| キーワード | ||||||||||||
| 主題 | KCC2 | |||||||||||
| キーワード | ||||||||||||
| 主題 | detrusor overactivity | |||||||||||
| キーワード | ||||||||||||
| 主題 | efferent nerve | |||||||||||
| キーワード | ||||||||||||
| 主題 | sacral parasympathetic nucleus | |||||||||||
| キーワード | ||||||||||||
| 主題 | spinal cord injury | |||||||||||
| 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 | |||||||||||
| その他のタイトル | ||||||||||||
| その他のタイトル | 脊髄損傷に伴う排尿筋過活動に対するKCC2 クロライドイオン・トランスポーター活性化の治療的作用 | |||||||||||
| その他のタイトル | ||||||||||||
| その他のタイトル | KCC2 DOWNREGULATION AND DETRUSOR OVERACTIVITY IN SCI MICE | |||||||||||
| 著者 |
渡邊, 恭平
× 渡邊, 恭平
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| 書誌情報 |
en : American Journal of Physiology-Renal Physiology 巻 324, 号 4, p. F353-F361, 発行日 2023-04-01 |
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| 出版者 | ||||||||||||
| 出版者 | American Physiological Society | |||||||||||
| 言語 | en | |||||||||||
| 権利 | ||||||||||||
| 言語 | en | |||||||||||
| 権利情報 | (C) 2023 the American Physiological Society | |||||||||||
| 権利 | ||||||||||||
| 言語 | en | |||||||||||
| 権利情報 | The full-text file will be made open to the public on 1 April 2024 in accordance with the publisher's policy. | |||||||||||
| 抄録 | ||||||||||||
| 内容記述タイプ | Abstract | |||||||||||
| 内容記述 | This study aimed to clarify whether the down regulation of K+-Cl−co-transporter 2 (KCC2) in the sacral parasympathetic nucleus (SPN) of the lumbosacral spinal cord, from which the efferent pathway innervating the bladder originates, causes cellular hyperexcitability and triggers detrusor overactivity (DO) in spinal cord injury (SCI). SCI was produced by the Th8-9 spinal cord transection in female C57BL/6 mice. At 4 weeks after SCI, CLP290, a KCC2 activator, was administered, and cystometry was performed. Thereafter, neuronal activity with c-fos staining and KCC2 expression in the cholinergic preganglionic parasympathetic neurons in the SPN were examined using immunohistochemistry. Firing properties of neurons in the SPN region were evaluated by extracellular recordings in spinal cord slice preparations. DO evident as non-voiding contractions (NVC) was significantly reduced by CLP290 treatment in SCI mice. The number of c-fos-positive cells and co-expression of c-fos in choline acetyltransferase (ChAT)-positive cells were decreased in the SPN region of SCI-CLP290 group vs. SCI-vehicle group. KCC2 immunoreactivity was present on the cell membrane of SPN neurons, and the normalized fluorescence intensity of KCC2 in ChAT-positive SPN neurons was decreased in SCI-vehicle group, vs. SI-vehicle group, but recovered in SCI-CLP290 group. Extracellular recordings showed that CLP290 suppressed the high frequency firing activity of SPN neurons in SCI mice. These results indicated that SCI-induced DO is associated with downregulation of KCC2 in preganglionic parasympathetic neurons, and that activation of KCC2 transporters can reduce DO, increase KCC2 expression in preganglionic parasympathetic neurons and decrease neuronal firing of SPN neurons in SCI mice. | |||||||||||
| 言語 | en | |||||||||||
| 抄録 | ||||||||||||
| 内容記述タイプ | Abstract | |||||||||||
| 内容記述 | NEW & NOTEWORTHY This study is the first report to suggest that activation of KCC2 chloride ion transporter may be a therapeutic modality for the treatment of SCI-induced DO by targeting bladder efferent pathways. |
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| 言語 | en | |||||||||||
| 学位名 | ||||||||||||
| 学位名 | 博士（医学） | |||||||||||
| 学位の区分 | ||||||||||||
| 内容記述 | dotoral | |||||||||||
| 学位の分野 | ||||||||||||
| 内容記述 | 医学系研究科 | |||||||||||
| 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 | 13802 | |||||||||||
| 学位授与機関名 | 浜松医科大学 | |||||||||||
| 学位授与年月日 | ||||||||||||
| 学位授与年月日 | 2023-03-16 | |||||||||||
| 学位授与番号 | ||||||||||||
| 学位授与番号 | 甲第948号 | |||||||||||
| ISSN | ||||||||||||
| 収録物識別子タイプ | PISSN | |||||||||||
| 収録物識別子 | 1931-857X | |||||||||||
| EISSN | ||||||||||||
| 収録物識別子タイプ | EISSN | |||||||||||
| 収録物識別子 | 1522-1466 | |||||||||||
| PubMed番号 | ||||||||||||
| 関連タイプ | isVersionOf | |||||||||||
| 識別子タイプ | PMID | |||||||||||
| 関連識別子 | 36656987 | |||||||||||
| 出版社DOI | ||||||||||||
| 関連タイプ | isVersionOf | |||||||||||
| 識別子タイプ | DOI | |||||||||||
| 関連識別子 | https://doi.org/10.1152/ajprenal.00271.2022 | |||||||||||
| 著者版フラグ | ||||||||||||
| 出版タイプ | AM | |||||||||||
| 出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||||||||
