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首页> 外文期刊>Cell and Tissue Research >Melatonin receptor deficiency decreases and temporally shifts ecto-5'-nucleotidase mRNA levels in mouse prosencephalon
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Melatonin receptor deficiency decreases and temporally shifts ecto-5'-nucleotidase mRNA levels in mouse prosencephalon

机译:褪黑素受体缺乏症减少并且在小鼠前脑中暂时改变ecto-5'-核苷酸酶mRNA水平

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Ecto-5'-nucleotidase (eN) is the major extracellular adenosine-producing ecto-enzyme in mouse brain. Via the production of adenosine, eN participates in many physiological and pathological processes, such as wakefulness, inflammation, nociception and neuroprotection. The mechanisms regulating the expression of eN are therefore of considerable neurobiological and clinical interest. Having previously described a modulatory effect of melatonin in the regulation of eN mRNA levels, we decided to analyze the melatonin receptor subtype involved in the regulation of eN mRNA levels by comparing eN mRNA patterns in melatonin-proficient transgenic mice lacking either the melatonin receptor subtype 1 (MT1 KO) or both melatonin receptor subtypes (MT1 and MT2; MT1/2 KO) with the corresponding melatonin-proficient wild-type (WT) controls. By means of radioactive in situ hybridization, eN mRNA levels were found to be diminished in both MT1 and MT1/2 KO mice compared with WT controls suggesting stimulatory impacts of melatonin receptors on eN mRNA levels. Whereas eN mRNA levels increased during the day and peaked at night in WT and MT1 KO mice, eN mRNA levels at night were reduced and the peak was shifted toward day-time in double MT1/2 KO mice. These data suggest that the MT2 receptor subtype may play a role in the temporal regulation of eN mRNA availability. Notably, day-time locomotor activity was significantly higher in MT1/2 KO compared with WT mice. Our results suggest melatoninergic signaling as an interface between the purinergic system and the circadian system.
机译:Ecto-5'-核苷酸酶(eN)是小鼠大脑中主要的细胞外腺苷产生外切酶。通过产生腺苷,eN参与了许多生理和病理过程,例如清醒,炎症,伤害感受和神经保护。因此,调节eN表达的机制具有相当大的神经生物学和临床意义。先前已经描述了褪黑激素在调节eN mRNA水平中的调节作用,我们决定通过比较缺乏褪黑激素受体亚型1的褪黑激素熟练的转基因小鼠中的eN mRNA模式来分析参与调节eN mRNA水平的褪黑激素受体亚型。 (MT1 KO)或两种褪黑素受体亚型(MT1和MT2; MT1 / 2 KO)以及相应的褪黑素熟练野生型(WT)对照。通过放射性原位杂交,与WT对照相比,MT1和MT1 / 2 KO小鼠的eN mRNA水平降低,提示褪黑激素受体对eN mRNA水平有刺激作用。 WT和MT1 KO小鼠的eN mRNA水平在白天增加并在夜间达到峰值,而双MT1 / 2 KO小鼠的eN mRNA水平在夜间降低,并且该峰向白天移动。这些数据表明,MT2受体亚型可能在eN mRNA可用性的时间调节中起作用。值得注意的是,与WT小鼠相比,MT1 / 2 KO的日间运动能力明显更高。我们的结果表明,黑色素能信号作为嘌呤能系统和昼夜节律系统之间的接口。

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