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正常个体及亨廷顿舞蹈症患者纹状体中间神经元的化学解剖学

Chemical anatomy of striatal interneurons in normal individuals and in patients with Huntington's disease.

作者信息

Cicchetti F, Prensa L, Wu Y, Parent A

机构信息

Centre de Recherche Université Laval Robert-Giffard, 2601 Chemin de la Canardière, Local F-6500, Québec, G1J 2G3, Beauport, Canada.

出版信息

Brain Res Brain Res Rev. 2000 Nov;34(1-2):80-101. doi: 10.1016/s0165-0173(00)00039-4.

DOI:10.1016/s0165-0173(00)00039-4
PMID:11086188
Abstract

This paper reviews the major anatomical and chemical features of the various types of interneurons in the human striatum, as detected by immunostaining procedures applied to postmortem tissue from normal individuals and patients with Huntington's disease (HD). The human striatum harbors a highly pleomorphic population of aspiny interneurons that stain for either a calcium-binding protein (calretinin, parvalbumin or calbindin D-28k), choline acetyltransferase (ChAT) or NADPH-diaphorase, or various combinations thereof. Neurons that express calretinin (CR), including multitudinous medium and a smaller number of large neurons, are by far the most abundant interneurons in the human striatum. The medium CR+ neurons do not colocalize with any of the known chemical markers of striatal neurons, except perhaps GABA, and are selectively spared in HD. Most large CR+ interneurons display ChAT immunoreactivity and also express substance P receptors. The medium and large CR+ neurons are enriched with glutamate receptor subunit GluR2 and GluR4, respectively. This difference in AMPA GluR subunit expression may account for the relative resistance of medium CR+ neurons to glutamate-mediated excitotoxicity that may be involved in HD. The various striatal chemical markers display a highly heterogeneous distribution pattern in human. In addition to the classic striosomes/matrix compartmentalization, the striosomal compartment itself is composed of a core and a peripheral region, each subdivided by distinct subsets of striatal interneurons. A proper knowledge of all these features that appear unique to humans should greatly help our understanding of the organization of the human striatum in both health and disease states.

摘要

本文回顾了通过对正常个体和亨廷顿舞蹈病(HD)患者的尸检组织进行免疫染色程序所检测到的人类纹状体中各类中间神经元的主要解剖学和化学特征。人类纹状体含有高度多形性的无棘中间神经元群体,这些神经元可被钙结合蛋白(钙视网膜蛋白、小白蛋白或钙结合蛋白D - 28k)、胆碱乙酰转移酶(ChAT)或NADPH - 黄递酶,或它们的各种组合染色。表达钙视网膜蛋白(CR)的神经元,包括众多中型神经元和少量大型神经元,是人类纹状体中迄今为止最为丰富的中间神经元。中型CR⁺神经元除了可能与GABA外,不与任何已知的纹状体神经元化学标记物共定位,并且在HD中选择性地得以保留。大多数大型CR⁺中间神经元显示ChAT免疫反应性,并且还表达P物质受体。中型和大型CR⁺神经元分别富含谷氨酸受体亚基GluR2和GluR4。AMPA GluR亚基表达的这种差异可能解释了中型CR⁺神经元对可能参与HD的谷氨酸介导的兴奋性毒性的相对抗性。各种纹状体化学标记物在人类中显示出高度异质性的分布模式。除了经典的纹状体小体/基质分区外,纹状体小体分区本身由一个核心和一个周边区域组成,每个区域又被不同的纹状体中间神经元亚群细分。对所有这些似乎是人类独有的特征的恰当了解,应该会极大地帮助我们理解人类纹状体在健康和疾病状态下的组织情况。

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