STUDY OBJECTIVE:\ud\udTo study whether sleep and circadian rhythm disturbances in patients with Huntington's disease (HD) arise from dysfunction of the body's master clock, the hypothalamic suprachiasmatic nucleus.\udDESIGN:\ud\udPostmortem cohort study.\udPATIENTS:\ud\udEight patients with HD and eight control subjects matched for sex, age, clock time and month of death, postmortem delay, and fixation time of paraffin-embedded hypothalamic tissue.\udMEASUREMENTS AND RESULTS:\ud\udUsing postmortem paraffin-embedded tissue, we assessed the functional integrity of the suprachiasmatic nucleus in patients with HD and control subjects by determining the expression of two major regulatory neuropeptides, vasoactive intestinal polypeptide and arginine vasopressin. Additionally, we studied melatonin 1 and 2 receptor expression. Compared with control subjects, the suprachiasmatic nucleus contained 85% fewer neurons immunoreactive for vasoactive intestinal polypeptide and 33% fewer neurons for arginine vasopressin in patients with HD (P = 0.002 and P = 0.027). The total amount of vasoactive intestinal polypeptide and arginine vasopressin messenger RNA was unchanged. No change was observed in the number of melatonin 1 or 2 receptor immunoreactive neurons.\udCONCLUSIONS:\ud\udThese findings indicate posttranscriptional neuropeptide changes in the suprachiasmatic nucleus of patients with HD, and suggest that sleep and circadian rhythm disorders in these patients may at least partly arise from suprachiasmatic nucleus dysfunction.
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机译:研究目的:\ ud \ ud用于研究亨廷顿氏病(HD)患者的睡眠和昼夜节律紊乱是否由机体下丘脑视交叉上枢神经功能障碍引起。 ud \ ud八名HD患者和八名对照受试者的性别,年龄,时钟时间和死亡月份,验尸延迟以及石蜡包埋的下丘脑组织的固定时间相匹配。\ ud测量和结果: ,我们通过确定两种主要调节性神经肽(血管活性肠多肽和精氨酸加压素)的表达,评估了HD患者和对照受试者的上交叉眼核的功能完整性。此外,我们研究了褪黑激素1和2受体的表达。与对照组相比,HD患者的上视交叉神经核对血管活性肠多肽的免疫反应神经元减少了85%,对精氨酸加压素的神经元减少了33%(P = 0.002和P = 0.027)。血管活性肠多肽和精氨酸加压素信使RNA的总量不变。褪黑素1或2受体免疫反应性神经元的数量未见变化。至少部分源于视交叉上核功能障碍。
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