Melatonin is a pleiotrophic hormone, synthesised primarily by the pineal gland under the control of the suprachiasmatic nuclei (SCN). It not only provides a hormonal signal of darkness but also has neuroprotective properties. Huntington's disease (HD) is a progressive neurodegenerative disorder characterised by abnormal motor, cognitive and psychiatric symptoms. There is growing evidence, particularly from animal models, that circadian rhythms may also be disturbed in HD. We measured two circadian-regulated hormones, melatonin and cortisol, in plasma samples collected around-the-clock from normal and presymptomatic transgenic HD sheep (Ovis aries) at 5 and 7 years of age, to assess SCN-driven rhythms and the effect of genotype, sex and age. Melatonin-related precursors and metabolites (tryptophan, serotonin, kynurenine) were also measured by liquid chromatography (LC)-mass spectrometry (MS). At 5 years of age in both rams and ewes, plasma melatonin levels were significantly elevated in HD sheep. In ewes measured 2 years later, there was still a significant elevation of nocturnal melatonin. Furthermore, the daytime baseline levels of melatonin were significantly higher in HD sheep. Since increased melatonin could have global beneficial effects on brain function, we suggest that the increased melatonin measured in presymptomatic HD sheep is part of an autoprotective response to mutant huntingtin toxicity that may account, at least in part, for the late onset of disease that characterises HD.

中文翻译：

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有症状的亨廷顿病绵羊（Ovis aries）中血浆褪黑激素增加：神经退行性疾病中的代偿性神经保护？

褪黑素是一种多营养激素，主要由松果体在视交叉上核（SCN）的控制下合成。它不仅提供黑暗的激素信号，而且具有神经保护特性。亨廷顿舞蹈病（HD）是一种进行性神经退行性疾病，其特征在于异常的运动，认知和精神病学症状。越来越多的证据，尤其是动物模型的证据表明，昼夜节律也可能在高清中受到干扰。我们测量了正常和有症状的转基因高清绵羊（Ovis aries）在5和7岁时全天采集的血浆样品中两种昼夜节律调节的激素，褪黑激素和皮质醇，以评估SCN驱动的节律和基因型，性别和年龄。褪黑激素相关的前体和代谢产物（色氨酸，5-羟色胺，还通过液相色谱（LC）-质谱（MS）测量了尿嘧啶核苷。在公羊和母羊中，在5岁时，HD绵羊的血浆褪黑激素水平显着升高。在2年后测量的母羊中，夜间褪黑激素仍显着升高。此外，HD绵羊的白天褪黑激素基线水平显着更高。由于增加的褪黑激素可能对脑功能具有整体有益的作用，因此我们建议在有症状的高清绵羊中测得的褪黑激素增加是对突变亨廷顿蛋白毒性的自我保护反应的一部分，这至少可以部分解释特征在于疾病晚期的特征高清。在2年后测量的母羊中，夜间褪黑激素仍显着升高。此外，HD绵羊的白天褪黑激素基线水平显着更高。由于褪黑激素增加可能对脑功能有整体有益影响，因此我们建议在症状发生前高清绵羊中测得的褪黑激素增加是对突变亨廷顿蛋白毒性的自我保护反应的一部分，这至少可以部分解释特征在于疾病晚期的特征高清。在2年后测量的母羊中，夜间褪黑激素仍显着升高。此外，HD绵羊的白天褪黑激素基线水平显着更高。由于褪黑激素增加可能对脑功能有整体有益影响，因此我们建议在症状发生前高清绵羊中测得的褪黑激素增加是对突变亨廷顿蛋白毒性的自我保护反应的一部分，这至少可以部分解释特征在于疾病晚期的特征高清。