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人类脑室下区的多巴胺能神经支配:亨廷顿舞蹈病与帕金森病的比较

Dopaminergic innervation of the human subventricular zone: a comparison between Huntington's chorea and Parkinson's disease.

作者信息

Parent Martin, Bédard C, Pourcher E

机构信息

Centre de recherche de l'Institut universitaire en santé mentale de Québec, Department of Psychiatry and Neuroscience, Faculty of Medicine, Université Laval Quebec City, QC, Canada.

出版信息

Am J Neurodegener Dis. 2013 Sep 18;2(3):221-7. eCollection 2013.

Abstract

The subventricular zone retains its neurogenic capacity throughout life and, as such, is often considered a potential source for endogenous repair in neurodegenerative disorders. Because dopamine is believed to stimulate adult neurogenesis, we looked for possible variations in the dopaminergic innervation of the subventricular zone between cases of Huntington's chorea and Parkinson's diseases. Antibodies against tyrosine hydroxylase (TH) and proliferating cell nuclear antigen (PCNA) were used as specific markers of dopaminergic axons and cell proliferating activity, respectively. The immunohistochemical approach was applied to postmortem tissue from 2 Parkinson's disease cases, 4 Huntington's disease cases, along with age-matched controls. The immunostaining was revealed with either diaminobenzidine or fluorescent-conjugated secondary antibodies. Optical density measurements were made along the entire dorso-ventral extent of the caudate nucleus. An intense TH+ zone was detected along the ventricular border of the caudate nucleus in Huntington's disease cases, but not in patients with Parkinson's disease or age-matched controls. This thin (287±38 μm) paraventricular zone was composed of numerous small and densely packed dopamine axon varicosities and overlapped the deep layers of the subventricular zone. Its immunoreactivity was 47±8% more intense than that of adjacent striatal areas. The dopamine innervation of the subventricular zone is strikingly massive in Huntington's chorea compared to Parkinson's disease, a finding that concurs with the marked increase in neurogenesis noted in the subventricular zone of Huntington's disease patients. This finding suggests that dopamine plays a crucial role in mechanisms designed to compensate for the massive striatal neuronal losses that occur in Huntington's disease.

摘要

室下区终生保留其神经发生能力,因此,它常被视为神经退行性疾病内源性修复的潜在来源。由于多巴胺被认为能刺激成体神经发生,我们研究了亨廷顿舞蹈症和帕金森病患者的室下区多巴胺能神经支配是否存在差异。分别使用抗酪氨酸羟化酶(TH)和增殖细胞核抗原(PCNA)的抗体作为多巴胺能轴突和细胞增殖活性的特异性标志物。免疫组化方法应用于2例帕金森病患者、4例亨廷顿舞蹈症患者的尸检组织以及年龄匹配的对照。免疫染色用二氨基联苯胺或荧光偶联二抗显示。在尾状核的整个背腹范围内进行光密度测量。在亨廷顿舞蹈症患者中,在尾状核的室周边界检测到一个强烈的TH+区,但在帕金森病患者或年龄匹配的对照中未检测到。这个薄的(287±38μm)室旁区由许多小而密集的多巴胺轴突膨体组成,与室下区的深层重叠。其免疫反应性比相邻纹状体区域强47±8%。与帕金森病相比,亨廷顿舞蹈症患者室下区的多巴胺神经支配明显大量增加,这一发现与亨廷顿舞蹈症患者室下区神经发生显著增加的情况一致。这一发现表明,多巴胺在旨在补偿亨廷顿舞蹈症中发生的大量纹状体神经元损失的机制中起关键作用。

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