Chen Q, Veenman C L, Reiner A
Department of Anatomy & Neurobiology, University of Tennessee-Memphis 38163, USA.
Neuroscience. 1996 Aug;73(3):715-31. doi: 10.1016/0306-4522(96)00011-5.
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.
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著的功能差异。因此，准确了解纹状体神经元上的亚基组成是理解纹状体神经元对兴奋性氨基酸选择性易损性的先决条件。在本研究中，我们使用免疫组织化学双标记方法在特定的纹状体神经元群体上定位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未被α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体亚基GluR1、GluR2/3和GluR4标记。然而，大多数胆碱能和生长抑素中间神经元（83.3%至100%）被N-甲基-D-天冬氨酸受体亚基NR1和海人酸受体亚基GluR5/6/7双标记。所有小白蛋白中间神经元都被GluR1和GluR4标记，96%的GluR1阳性神经元和95%的GluR4阳性神经元也被双标记为小白蛋白中间神经元。约一半的小白蛋白中间神经元与GluR2/3共定位，超过97%被NR1和GluR5/6/7标记。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被GluR1或GluR4免疫染色。相反，这些类型的投射神经元中每种的95%至100%被NR1、GluR2/3和GluR5/6/7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上存在差异。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/亚基上的明显差异支持这样一种观点，即谷氨酸受体表达机制的差异可能解释纹状体投射神经元对兴奋性毒性的选择性易损性，并且谷氨酸受体介导的兴奋性毒性可能参与纹状体神经退行性疾病。
