Sex Associated Differential Expressions of the Alternatively Spliced Variants mRNA of OPRM1 in Brain Regions of C57BL/6 Mouse
Sex Associated Differential Expressions of the Alternatively Spliced Variants mRNA of OPRM1 in Brain Regions of C57BL/6 Mouse
复制标题
C57BL/6小鼠脑区OPRM1选择性剪接变体mRNA的性别相关差异表达
DOI：
10.1159/000494644
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发表时间：
2018-01-01
影响因子：
--
通讯作者：
Lu, Zhigang
中科院分区：
文献类型：
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作者：
Liu, Anlong;Zhang, Han;Lu, Zhigang
背景/目的：阿片类药物是一种有效的镇痛药，但其临床应用受到性别相关副作用的限制，如药物耐受性、阿片类药物引起的痛觉过敏和戒断反应。OPRM1作为阿片类药物的主要受体，在啮齿动物和人类的阿片类药物药理过程中发挥重要作用。我们之前研究了阿片受体基因OPRM1，该基因具有数十种可能与阿片诱导作用相关的选择性剪接变体，并证明了这些剪接变体在四种近交系小鼠大脑区域的特异性表达。在一个菌株内，一些变异的区域表达模式相似，而另一些则相反。因此，我们的目标是找出性别差异和这些选择性剪接变体之间的关系。方法：本研究采用SYBR绿色定量PCR （qPCR）方法，在C57BL/6小鼠的特定脑区检测OPRM1剪接变异体mrna的表达。基线潜伏期、阿片诱导耐受性、镇痛和成瘾的性别差异通过甩尾试验、跳跃和统计分析来检测和确定。结果：雄性和雌性小鼠阿片受体基因剪接变异mRNA水平在脑区域间存在显著差异，提示OPRM1基因存在区域特异性选择性剪接，这与我们前期的研究结果一致。更重要的是，OPRM1剪接变体的完整mRNA表达谱也具有性别特异性，这表明性别对OPRM1选择性剪接有影响。结论：综上所述，雌雄小鼠基线潜伏期、阿片类药物耐受性、镇痛和身体依赖的差异可能与OPRM1基因的性别差异表达有关。(C) 2018作者：s . Karger AG，巴塞尔出版
Background/Aims: Opiates are potent analgesics but their clinical use is limited by sexassociated side effects, such as drug tolerance, opioid-induced hyperalgesia and withdrawal reaction. OPRM1, as the main receptor of opioids, plays an important role in the pharmacological process of opioids in rodents and human. We have previously investigated OPRM1, the mu opioid receptor gene, which have dozens of alternatively spliced variants probably correlating with opioid-induced effects in brain regions of four inbred mouse strains and demonstrated the strain-specific expressions of these splice variants. Also, within a strain, the regional expression patterns of some of the variants were similar while others were opposite. Thus, we are aiming to seek out the relationship between sex differences and these alternatively spliced variants. Methods: The present studies follow a SYBR green quantitative PCR (qPCR) which we had used before to examine the expression of OPRM1 splice variant mRNAs in selected brain regions of male and female C57BL/6 mice. Sex-associated differences in baseline latency, opioid-induced tolerance, analgesia and addiction were examined and determined by Tail-flick test, jumps and statistical analysis. Results: The mRNA levels of opioid receptor gene splice variants in male and female mice showed significant differences among the brain regions, implying region-specific alternative splicing of the OPRM1 gene, which was consistent with our previous study. More importantly, the complete mRNA expression profiles of the OPRM1 splice variants was also gender-specific, suggesting a sexual influence on OPRM1 alternative splicing. Conclusion: In brief, we put forward that the distinctions among baseline latency, opioid-induced tolerance, analgesia and physical dependence in male and female mice might correlate with sex associated differential expressions of OPRM1 gene. (C) 2018 The Author(s) Published by S. Karger AG, Basel