Cellular and subcellular mRNA localization of glutamate transporter isoforms GLT1a and GLT1b in rat brain by in situ hybridization
Cellular and subcellular mRNA localization of glutamate transporter isoforms GLT1a and GLT1b in rat brain by in situ hybridization
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DOI：
10.1002/cne.20737
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发表时间：
2005-11-07
影响因子：
2.5
通讯作者：
Rosenberg, PA
中科院分区：
文献类型：
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作者：
Berger, UV;DeSilva, TM;Rosenberg, PA
GLT1是前脑中主要的谷氨酸转运蛋白，存在于GLT1a和GLT1b两种剪接变异亚型中。虽然GLT1最初仅在星形胶质细胞中检测到，但我们最近证明GLT1a蛋白也在海马神经元中表达。在本研究中，采用非同位素原位杂交和变异特异性RNA探针检测了这两种同工异构体在大鼠脑中的mRNA分布模式。这两种亚型均在海马外的神经元亚群中表达，如大脑皮层第六层或嗅结节中的神经元。与海马体的情况一样，GLT1a也是这些区域神经元的主要转录本。两种GLT1亚型在整个大脑的星形胶质细胞中广泛表达。GLT1a mRNA在星形胶质细胞中的表达在海马亚区和其他区域的标记强度存在明显差异，而GLT1b在星形胶质细胞中的表达相对均匀。在亚细胞水平上，GLT1a mRNA主要在星形胶质细胞过程中表达，而GLT1b mRNA更多地局限于星形胶质细胞细胞体。这两种异构体在皮层下器官和第三脑室的伸长细胞中表现出相似的分布。然而，GLT1在松果体和视网膜中的表达主要是由于GLT1b，而GLT1a在小脑的伯格曼胶质细胞中表达更为强烈。这些发现表明，两种GLT1亚型的表达受到不同机制的调控。此外，这两种异构体的功能可能受到不同的调控过程。
GLT1, the predominant glutamate transporter of the forebrain, exists in two splice variant isoforms, i.e., GLT1a and GLT1b. Although GLT1 was originally detected only in astrocytes, we have recently demonstrated that GLT1a protein is expressed by neurons in the hippocampus as well. In the present study, the mRNA distribution patterns for the two isoforms were examined throughout the rat brain by using nonisotopic in situ hybridization and variant-specific RNA probes. Both isoforms were expressed in neuronal subgroups outside the hippocampus, such as in the cerebral cortex layer VI, or the neurons in the olfactory tubercle. As was the case in the hippocampus, GLT1a was the predominant transcript in neurons in these regions as well. Both GLT1 isoforms were widely expressed in astrocytes throughout the brain. GLT1a mRNA expression in astrocytes showed noticeable variation in labeling intensity in subregions of the hippocampus and other areas, whereas GLT1b expression in astrocytes was relatively homogeneous. On the subcellular level, GLT1a mRNA was expressed primarily in astrocyte processes, whereas GLT1b mRNA was more restricted to the astrocyte cell body. The two isoforms showed similar distributions in the subfornical organ and in tanycytes of the third ventricle. However, GLT1 expression in the pineal gland and the retina was due primarily to GLT1b, whereas GLT1a was more strongly expressed in Bergman glia in the cerebellum. These findings suggest that the expression of the two GLT1 isoforms is regulated by different mechanisms. Moreover, the function of the two isoforms may be subject to different regulatory processes.