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The mitochondrial calcium uniporter contributes to morphine tolerance through pCREB and CPEB1 in rat spinal cord dorsal horn
https://asahikawa-med.repo.nii.ac.jp/records/6256
https://asahikawa-med.repo.nii.ac.jp/records/6256f94ab2d2-db57-466a-8205-8d321eb03430
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
7548.pdf (11.0 MB)
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| Item type | 学位論文 / Thesis or Dissertation_02(1) | |||||||||
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| 公開日 | 2021-04-23 | |||||||||
| タイトル | ||||||||||
| タイトル | The mitochondrial calcium uniporter contributes to morphine tolerance through pCREB and CPEB1 in rat spinal cord dorsal horn | |||||||||
| 言語 | en | |||||||||
| 言語 | ||||||||||
| 言語 | eng | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | CPEB | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | CREB | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | calcium | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | mitochondrial calcium uniporter | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | morphine | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | opioid tolerance | |||||||||
| キーワード | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | opioids | |||||||||
| 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（別言語等）のタイトル | ||||||||||
| その他のタイトル | ラット脊髄後角でミトコンドリアカルシウムユニポータはpCREB,CPEB1を介してモルヒネ耐性に関与する | |||||||||
| 言語 | ja | |||||||||
| 著者 |
髙橋, 桂哉
× 髙橋, 桂哉
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| 著者 ローマ字 | ||||||||||
| Takahashi, keiya | ||||||||||
| bibliographic_information |
en : British Journal of Anaesthesia 巻 123, 号 2, p. e226-e238, 発行日 2019-08-01 |
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| DOI | ||||||||||
| 識別子タイプ | DOI | |||||||||
| 関連識別子 | 10.1016/j.bja.2019.05.027 | |||||||||
| 識別番号 その他 | ||||||||||
| 内容記述タイプ | Other | |||||||||
| 内容記述 | PMID: 31253357 | |||||||||
| dissertation_number | ||||||||||
| 学位授与番号 | 甲539 | |||||||||
| 学位授与年月日 | ||||||||||
| 学位授与年月日 | 2020-03-25 | |||||||||
| 学位名 | ||||||||||
| 言語 | ja | |||||||||
| 学位名 | 博士（医学） | |||||||||
| item_10_degree_grantor_32 | ||||||||||
| 言語 | ja | |||||||||
| 学位授与機関名 | 旭川医科大学 | |||||||||
| item_10_description_33 | ||||||||||
| 内容記述タイプ | Abstract | |||||||||
| 内容記述 | Background: The long-term use of opioid analgesics is limited by the development of unwanted side-effects, such as tolerance. The molecular mechanisms of morphine anti-nociceptive tolerance are still unclear. The mitochondrial calcium uniporter (MCU) is involved in painful hyperalgesia, but the role of MCU in morphine tolerance has not been uncharacterised. \nMethods: Rats received intrathecal injection of morphine for 7 days to induce morphine tolerance. The mechanical withdrawal threshold was measured using von Frey filaments, and thermal latency using the hotplate test. The effects of an MCU inhibitor, antisense oligodeoxynucleotide against cyclic adenosine monophosphate response element (CRE)-binding protein (CREB) or cytoplasmic polyadenylation element-binding protein 1 (CPEB1) in morphine tolerance were examined. \nResults: Spinal morphine tolerance was associated with an increased expression of neuronal MCU, phospho-CREB (pCREB), and CPEB1 in the spinal cord dorsal horn. MCU inhibition increased the mechanical threshold and thermal latency, and reduced the accumulation of mitochondrial calcium in morphine tolerance. Intrathecal antisense oligodeoxynucleotide against CREB or CPEB1 restored the anti-nociceptive effects of morphine compared with mismatch oligodeoxynucleotide in von Frey test and hotplate test. Chromatin immunoprecipitation with quantitative PCR assay showed that CREB knockdown reduced the interaction of pCREB with the ccdc109a gene (encoding MCU expression) promoter and decreased the MCU mRNA transcription. RNA immunoprecipitation assay suggested that CPEB1 binds to the MCU mRNA 3' untranslated region. CPEB1 knockdown decreased the expression of MCU protein. \nConclusions: These findings suggest that spinal MCU is regulated by pCREB and CPEB1 in morphine tolerance, and that inhibition of MCU, pCREB, or CPEB1 may be useful in preventing the development of opioid tolerance. |
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| item_10_description_37 | ||||||||||
| 内容記述タイプ | Other | |||||||||
| 内容記述 | application/pdf | |||||||||
| 言語 | en | |||||||||
| 出版タイプ | ||||||||||
| 出版タイプ | VoR | |||||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||
| item_10_description_41 | ||||||||||
| 内容記述タイプ | Other | |||||||||
| 内容記述 | application/pdf | |||||||||
