The mitochondrial calcium uniporter contributes to morphine tolerance through pCREB and CPEB1 in rat spinal cord dorsal horn （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）

• Material Type: 博士論文
• Title: The mitochondrial calcium uniporter contributes to morphine tolerance through pCREB and CPEB1 in rat spinal cord dorsal horn （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）
• Volume: 123 2
• Author/Editor: 髙橋, 桂哉
• Author Heading: 髙橋, 桂哉
• Publication Date: 2019-08; 123 2
• Publication Date (W3CDTF): 2019-08
• Periodical title: British Journal of Anaesthesia
• Degree grantor/type: 旭川医科大学
• Date Granted: 2020-03-25
• Date Granted (W3CDTF): 2020-03-25
• Dissertation Number: 甲第539号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第539号
• Text Language Code: eng
• Subject Heading: CPEB; CREB; calcium; mitochondrial calcium uniporter; morphine; opioid tolerance; opioids
• Target Audience: 一般
• Note (General): type:application/pdf; 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.Methods: 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.Results: 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.Conclusions: 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.; identifier:PMID: 31253357
• DOI: info:doi/10.1016/j.bja.2019.05.027; https://doi.org/info:doi/10.1016/j.bja.2019.05.027
• Persistent ID (NDL): info:ndljp/pid/11671511; https://dl.ndl.go.jp/pid/11671511
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2021-05-16T23:51:55+09:00
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://amcor.asahikawa-med.ac.jp/modules/xoonips/detail.php?id=20200325_K539
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp