Expression of the glial glutamate transporter EAAT2 in the human CNS: an immunohistochemical study
Expression of the glial glutamate transporter EAAT2 in the human CNS: an immunohistochemical study
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DOI：
10.1016/s0169-328x(97)00233-7
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发表时间：
1997-12-01
期刊：
影响因子：
--
通讯作者：
Shaw, PJ
中科院分区：
文献类型：
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作者：
Milton, ID;Banner, SJ;Shaw, PJ
谷氨酸转运体在终止突触后受体的兴奋性谷氨酸能信号和保护神经元免受兴奋性毒性作用以及补充谷氨酸能突触的神经递质供应中起重要作用。谷氨酸转运体的分布和密度可能是谷氨酸介导的损伤易感性的重要决定因素。有新的证据表明，谷氨酸转运体功能障碍可能存在于运动神经元疾病（MND）。在这项研究中，一个单克隆抗体，适用于免疫组织化学（IHC）在人类死后组织，产生的人星形胶质细胞谷氨酸转运蛋白EAAT 2（兴奋性氨基酸转运蛋白2）。用EAAT 2抗体对人皮质组织匀浆进行Western印迹，在66 kDa处产生离散条带。对人CNS中EAAT 2蛋白的表达进行详细的IHC分析。EAAT 2仅定位于星形胶质细胞，在尾状核、Meynert基底核、脊髓腹侧缘、大脑皮质和海马中优先表达，但在许多其他CNS区域中表达水平较低。运动神经元组容易在MND神经变性出现独特的广泛，粗糙，强烈的免疫反应性周围胶质细胞的配置文件包围。运动神经元组，往往是备用的MND，如那些存在于眼神经核，表现出较低的EAAT 2的表达，较少的体周配置文件。EAAT2抗体将提供一个有用的工具，以增加我们的EAAT2的兴奋性神经传递在健康和疾病状态的作用的理解。(C)1997年Elsevier Science B.V.
Glutamate transporters play an essential role in terminating the excitatory glutamatergic signal at post-synaptic receptors and in protecting neurones from excitotoxic effects, as well as replenishing the neurotransmitter supply at glutamatergic synapses. The distribution and density of glutamate transporters may be important determinants of vulnerability to glutamate-mediated injury. There is emerging evidence that glutamate transporter dysfunction may be present in motor neurone disease (MND). In this study, a monoclonal antibody, suitable for immunohistochemistry (IHC) in human post-mortem tissue, was produced to the human astrocytic glutamate transporter EAAT2 (excitatory amino acid transporter 2). Western blotting of homogenates of human cortical tissue with the EAAT2 antibody produced a discrete band at 66 kDa. Detailed IHC analysis of the expression of the EAAT2 protein in the human CNS was undertaken. EAAT2 was exclusively localised to astrocytes, with preferential expression in the caudate nucleus, nucleus basalis of Meynert, spinal ventral hem, cerebral cortex and hippocampus, but with lower levels of expression throughout many other CNS regions. Motor neurone groups vulnerable to neurodegeneration in MND appeared distinctive in being surrounded by extensive, coarse, strongly immunoreactive perisomatic glial profiles. Motor neurone groups which tend to be spared in MND, such as those present in the oculomotor nucleus, showed a lower expression of EAAT2, with fewer perisomatic profiles. The EAAT2 antibody will provide a useful tool for increasing our understanding of the role of EAAT2 in excitatory neurotransmission in health and disease states. (C) 1997 Elsevier Science B.V.