Changes in key hypothalamic neuropeptide populations in Huntington disease revealed by neuropathological analyses
Changes in key hypothalamic neuropeptide populations in Huntington disease revealed by neuropathological analyses
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DOI：
10.1007/s00401-010-0742-6
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发表时间：
2010-12-01
影响因子：
12.7
通讯作者：
Petersen, Asa
中科院分区：
文献类型：
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作者：
Gabery, Sanaz;Murphy, Karen;Petersen, Asa
亨廷顿病 (HD) 是一种致命的神经退行性疾病，由 HD 基因中 CAG 重复序列的扩增引起。集中在基底神经节的变性被认为是导致特征性精神症状、认知能力下降和运动功能障碍的原因。然而，HD 早期情绪和代谢的稳态控制受到干扰，重点研究发现 HD 患者下丘脑外侧的食欲素（下丘脑分泌素）神经元缺失。对可能涉及的其他下丘脑细胞群的评估有限。在这项研究中，我们使用无偏见的体视学方法，与健康对照者相比，对 HD 患者下丘脑表达神经肽的神经元进行了量化，这些神经元可调节代谢和情绪。我们证实了 HD 中表达食欲素的神经元的丧失，并揭示了同一患者中其他神经元群的肽表达的显着差异。表达催产素和加压素的神经元分别减少了 45% 和 24%，而表达可卡因和安非他明调节转录物 (CART) 的神经元数量增加了 30%。下丘脑中 CART 表达的增加与之前的一项研究一致，该研究显示 HD 患者脑脊液中 CART 水平增加。表达神经肽Y的神经元的数量没有差异。这些结果表明，已知调节代谢和情绪的下丘脑神经元的肽表达发生了显着且特异的变化。它们可能在 HD 精神症状和代谢紊乱的发展中发挥重要作用，并可能为治疗干预提供潜在的目标。
Huntington disease (HD) is a fatal neurodegenerative disorder caused by expansion of a CAG repeat in the HD gene. Degeneration concentrating in the basal ganglia has been thought to account for the characteristic psychiatric symptoms, cognitive decline and motor dysfunction. However, the homeostatic control of emotions and metabolism are disturbed early in HD, and focused studies have identified a loss of orexin (hypocretin) neurons in the lateral hypothalamus in HD patients. There has been limited assessment of other hypothalamic cell populations that may be involved. In this study, we quantified the neuropeptide-expressing hypothalamic neurons known to regulate metabolism and emotion in patients with HD compared to healthy controls using unbiased stereological methods. We confirmed the loss of orexin-expressing neurons in HD and revealed substantial differences in the peptide expression of other neuronal populations in the same patients. Both oxytocin- and vasopressin-expressing neurons were decreased by 45 and 24%, respectively, while the number of cocaine- and amphetamine-regulated transcript (CART)-expressing neurons was increased by 30%. The increased expression of CART in the hypothalamus is consistent with a previous study showing increased CART levels in cerebrospinal fluid from HD patients. There was no difference in the numbers of neuropeptide Y-expressing neurons. These results show significant and specific alterations in the peptide expression of hypothalamic neurons known to regulate metabolism and emotion. They may be important in the development of psychiatric symptoms and metabolic disturbances in HD, and may provide potential targets for therapeutic interventions.