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首页> 外文期刊>Molecular pain >AMP-activated kinase and the endogenous endocannabinoid system might contribute to antinociceptive effects of prolonged moderate caloric restriction in mice
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AMP-activated kinase and the endogenous endocannabinoid system might contribute to antinociceptive effects of prolonged moderate caloric restriction in mice

机译：AMP激活的激酶和内源性内源性大麻素系统可能有助于延长小鼠中度热量限制的镇痛作用

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Caloric restriction is associated with broad therapeutic potential in various diseases and an increase in health and life span. In this study, we assessed the impact of caloric restriction on acute and inflammatory nociception in mice, which were either fed ad libitum or subjected to caloric restriction with 80% of the daily average for two weeks. The behavioral tests revealed that inflammatory nociception in the formalin test and in zymosan-induced mechanical hypersensitivity were significantly decreased when mice underwent caloric restriction. As potential mediators of the diet-induced antinociception, we assessed genes typically induced by inflammatory stimuli, AMP-activated kinase, and the endocannabinoid system which have all already been associated with nociceptive responses. Zymosan-induced inflammatory markers such as COX-2, TNFα, IL-1β, and c-fos in the spinal cord were not altered by caloric restriction. In contrast, AMPKα2 knock-out mice showed significant differences in comparison to C57BL/6 mice and their respective wild type littermates by missing the antinociceptive effects after caloric restriction. Endocannabinoid levels of anandamide and 2-arachidonyl glyceroldetermined in serum by LC-MS/MS were not affected by either caloric restriction alone or in combination with zymosan treatment. However, cannabinoid receptor type 1 expression in the spinal cord, which was not altered by caloric restriction in control mice, was significantly increased after caloric restriction in zymosan-induced paw inflammation. Since increased cannabinoid receptor type 1 signaling might influence AMP-activated kinase activity, we analyzed effects of anandamide on AMP-activated kinase in cell culture and observed a significant activation of AMP-activated kinase. Thus, endocannabionoid-induced AMP-activated kinase activation might be involved in antinociceptive effects after caloric restriction. Our data suggest that caloric restriction has an impact on inflammatory nociception which might involve AMP-activated kinase activation and an increased activity of the endogenous endocannabinoid system by caloric restriction-induced cannabinoid receptor type 1 upregulation.
机译：热量限制与多种疾病的广泛治疗潜力以及健康和寿命的增加相关。在这项研究中，我们评估了热量限制对小鼠急性和炎症伤害感受的影响，这些小鼠可以随意喂养或以每日平均80％的热量限制两周进行热量限制。行为测试表明，当小鼠进行热量限制时，福尔马林测试和酵母聚糖诱导的机械性超敏反应中的炎症伤害感受明显降低。作为饮食诱导的抗伤害感受的潜在介质，我们评估了通常由炎症刺激，AMP激活激酶和内源性大麻素系统诱导的基因，这些基因均已经与伤害反应相关。酵母聚糖诱导的炎症标记如脊髓中的COX-2，TNFα，IL-1β和c-fos不受热量限制的影响。相反，与C57BL / 6小鼠及其相应的野生型同窝幼仔相比，AMPKα2剔除小鼠由于缺乏热量限制后的抗伤害感受作用而显示出显着差异。 LC-MS / MS测定血清中大麻素的内在大麻素水平和2-花生四烯酸甘油酯水平不受单独热量限制或与酵母聚糖处理联合使用的影响。但是，在酵母聚糖诱导的爪发炎中热量限制后，脊髓中的大麻素受体1型表达没有受到热量限制的改变，而在对照小鼠中并未显着增加。由于增加的1型大麻素受体信号传导可能会影响AMP激活的激酶活性，因此我们在细胞培养物中分析了anandamide对AMP激活的激酶的影响，并观察到AMP激活的激酶的显着激活。因此，热量限制后，内源性大麻素诱导的AMP激活的激酶激活可能参与了抗伤害感受的作用。我们的数据表明，热量限制会对炎症伤害感受产生影响，这可能涉及AMP激活的激酶激活以及热量限制诱导的1型大麻素受体上调引起的内源性内源性大麻素系统活性增加。

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