Cellular expression of ionotropic glutamate receptor subunits on specific striatal neuron types and its implication for striatal vulnerability in glutamate receptor-mediated excitotoxicity
Cellular expression of ionotropic glutamate receptor subunits on specific striatal neuron types and its implication for striatal vulnerability in glutamate receptor-mediated excitotoxicity
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DOI：
10.1016/0306-4522(96)00011-5
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发表时间：
1996-08-01
期刊：
影响因子：
3.3
通讯作者：
Reiner, A
中科院分区：
文献类型：
--
作者：
Chen, Q;Veenman, CL;Reiner, A
谷氨酸受体由亚型特异性亚基组成。受体精确亚基组成的变化可能导致显着的功能差异。因此，准确了解纹状体神经元的亚基组成是了解纹状体神经元对兴奋性氨基酸的选择性脆弱性的先决条件。在本研究中，我们使用免疫组织化学双标记方法来定位特定纹状体神经元群体上的离子型谷氨酸受体亚基（NMDAR1、GluR1、GluR2/3、GluR4 和 GluR5/6/7）。我们的结果表明，纹状体胆碱能和生长抑素中间神经元没有标记α-氨基-3-羟基-5-甲基-4-异恶唑-丙酸酯、受体亚基GluR1、GluR2/3和GluR4。然而，大多数胆碱能和生长抑素中间神经元（83.3％至100％）被双重标记为N-甲基-D-天冬氨酸受体亚基NR1和红藻氨酸受体亚基GluR5/6/7。所有小清蛋白中间神经元都标记为 GluR1 和 GluR4，96% GluR1 阳性和 95% GluR4 阳性神经元也被双重标记为小清蛋白中间神经元。大约一半的小清蛋白中间神经元与 GluR2/3 共定位，超过 97% 的中间神经元被标记为 NR1 和 GluR5/6/7。在纹状体投射神经元中，脑啡肽阳性（主要是纹状体苍白球）神经元、纹状体黑质神经元（主要是 P 物质阳性）和钙结合蛋白阳性基质神经元未进行 GluR1 或 GluR4 免疫染色。相比之下，每种类型的投射神经元中的 95% 到 100% 都带有 NR1、GluR2/3 和 GluR5/6/7 的双标记。我们的结果表明，纹状体神经元类型在离子型谷氨酸受体亚基和亚型的表达方面有所不同。纹状体中间神经元和投射神经元在离子型谷氨酸受体亚型/亚基中的明显差异支持了以下观点：差异性谷氨酸受体表达机制可能解释了纹状体投射神经元对兴奋性毒性的选择性脆弱性，并且谷氨酸受体介导的兴奋性毒性可能与纹状体神经退行性疾病有关。版权所有 (C) 1996 IBRO。
Glutamate receptors are composed of subtype-specific subunits. Variation in the precise subunit composition of a receptor may result in significant functional differences. Thus, a precise knowledge of subunit composition on striatal neurons is a prerequisite for understanding the selective vulnerability of striatal neurons to excitatory amino acids. In the present study, we used an immunohistochemical double-labelling approach to localize ionotropic glutamate receptor subunits (NMDAR1, GluR1, GluR2/3, GluR4 and GluR5/6/7) on specific striatal neuron populations. Our results showed that striatal cholinergic and somatostatin interneurons were not labelled for the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate, receptor subunits GluR1, GluR2/3 and GluR4. Most cholinergic and somatostatin interneurons (83.3% to 100%), however, were double-labelled for the N-methyl-D-aspartate receptor subunit NR1 and kainic acid receptor subunits GluR5/6/7. All parvalbumin interneurons were labelled for GluR1 and GluR4, and 96% GluR1 positive and 95% GluR4 positive neurons were also double-labelled as parvalbumin interneurons. About half of all parvalbumin interneurons co-localized with GluR2/3, and over 97% were labelled for NR1 and GluR5/6/7. Among striatal projection neurons, enkephalin-positive (mainly striatopallidal) neurons, striatonigral neurons (mainly substance P-positive) and calbindin-positive matrix neurons were not immunostained for GluR1 or GluR4. In contrast, 95% to 100% of each of these types of projection neurons were double-labelled for NR1, GluR2/3 and GluR5/6/7.Our results demonstrate that striatal neuron types differ in their expression of ionotropic glutamate receptor subunits and subtypes. The clear difference between striatal interneurons and projection neurons in ionotropic glutamate receptor subtypes/subunits supports the idea that differential glutamate receptor expression mechanism may account for the selective vulnerability of striatal projection neurons to excitotoxicity, and that glutamate receptor-mediated excitotoxicity may be involved in the striatal neurodegenerative diseases. Copyright (C) 1996 IBRO.