Defects in the striatal neuropeptide Y system in X-linked dystonia-parkinsonism
Defects in the striatal neuropeptide Y system in X-linked dystonia-parkinsonism
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DOI：
10.1093/brain/awt084
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发表时间：
2013-05-01
期刊：
影响因子：
14.5
通讯作者：
Kaji, Ryuji
中科院分区：
文献类型：
--
作者：
Goto, Satoshi;Kawarai, Toshitaka;Kaji, Ryuji
神经肽Y是一种新的生物活性物质，在调节神经发生和神经递质释放中起作用，从而对神经退行性变发挥保护作用。使用一个敏感的免疫组化方法与酪胺信号放大协议，我们进行了尸检分析，以确定神经肽Y在神经系统正常的个人和患者的纹状体定位配置文件与X连锁肌张力障碍帕金森氏症，主要代表的神经退行性疾病，主要涉及纹状体。所有接受检查的患者都被遗传学证实患有X连锁肌张力障碍-帕金森综合征。在正常人中，我们发现了神经肽Y阳性神经元和许多神经纤维标记的神经肽Y在纹状体的分散分布。特别令人感兴趣的是神经肽Y免疫反应性在纹状体隔室中的差异定位，相对于纹状体，神经肽Y标记在基质隔室中的密度提高。在X连锁肌张力障碍-帕金森综合征患者中，我们发现神经肽Y阳性细胞的数量显著减少，伴随着尾状核和壳核中神经纤维的明显丢失。X连锁肌张力障碍-帕金森综合征患者的脑室下区也缺乏神经肽Y标记，其中表达增殖细胞核抗原的祖细胞明显丢失。我们的结果表明，X连锁肌张力障碍-帕金森综合征患者的神经肽Y系统存在新纹状体缺陷，提示其可能与X连锁肌张力障碍-帕金森综合征中纹状体神经元进行性丧失的机制有关。
Neuropeptide Y is a novel bioactive substance that plays a role in the modulation of neurogenesis and neurotransmitter release, and thereby exerts a protective influence against neurodegeneration. Using a sensitive immunohistochemical method with a tyramide signal amplification protocol, we performed a post-mortem analysis to determine the striatal localization profile of neuropeptide Y in neurologically normal individuals and in patients with X-linked dystonia-parkinsonism, a major representative of the neurodegenerative diseases that primarily involve the striatum. All of the patients examined were genetically verified as having X-linked dystonia-parkinsonism. In normal individuals, we found a scattered distribution of neuropeptide Y-positive neurons and numerous nerve fibres labelled for neuropeptide Y in the striatum. Of particular interest was a differential localization of neuropeptide Y immunoreactivity in the striatal compartments, with a heightened density of neuropeptide Y labelling in the matrix compartment relative to the striosomes. In patients with X-linked dystonia-parkinsonism, we found a significant decrease in the number of neuropeptide Y-positive cells accompanied by a marked loss of their nerve fibres in the caudate nucleus and putamen. The patients with X-linked dystonia-parkinsonism also showed a lack of neuropeptide Y labelling in the subventricular zone, where a marked loss of progenitor cells that express proliferating cell nuclear antigen was found. Our results indicate a neostriatal defect of the neuropeptide Y system in patients with X-linked dystonia-parkinsonism, suggesting its possible implication in the mechanism by which a progressive loss of striatal neurons occurs in X-linked dystonia-parkinsonism.