Northington F J, Traystman R J, Koehler R C, Martin L J
Department of Pediatrics, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
J Neurobiol. 1999 Jun 15;39(4):515-26.
Glutamate transport is a primary mechanism for regulating extracellular levels of glutamate in the central nervous system. GLT1, the most abundant of the known high-affinity glutamate transporters, is found exclusively in astrocytes in adult brain of several species, but we and others have recently identified neurons that transiently express GLT1 protein in the developing brain. We now demonstrate the development of cell type specificity for GLT1 expression at 60, 71, and 136 days' gestation in the developing sheep brain (term = 145 days). At 60 and 71 days of gestation, GLT1 colocalizes with calbindin in Purkinje cells in the cerebellum, and this expression pattern has a novel distribution that is reminiscent of the parasagittal zebrin-like bands. GLT1 immunoreactivity simultaneously occurs in periventricular white matter, anterior commissure, and striatal white matter, dissipating by 136 days. GLT1 protein expression within astrocytes is developmentally regulated, appearing first in vimentin positive radial glia at 60 and 71 days and then switching to GFAP positive parenchymal and perivascular astrocytes at 136 days. Expression of GLT1 in subsets of vimentin-positive astrocytes persists in white matter but not in cortex. These results identify a novel compartmentation within cerebellar cortex and neuronal and axonal pathway localization of GLT1, suggesting the participation of this glutamate transporter in the development of the topographic organization of cerebellar cortex and a transient neuronal function for GLT1 in developing brain. In addition, GLT1 expression is highly plastic, being neither exclusively astroglial nor uniformly expressed in different populations of astrocytes during brain development.
谷氨酸转运是调节中枢神经系统细胞外谷氨酸水平的主要机制。GLT1是已知高亲和力谷氨酸转运体中最丰富的一种,在几种成年动物大脑的星形胶质细胞中特异性表达,但我们和其他人最近发现,在发育中的大脑中,有神经元会短暂表达GLT1蛋白。我们现在证明了在发育中的绵羊大脑(孕期145天)妊娠60、71和136天时GLT1表达的细胞类型特异性的发展。在妊娠60和71天时,GLT1与小脑浦肯野细胞中的钙结合蛋白共定位,这种表达模式具有一种新的分布,让人联想到矢状旁斑马样条纹。GLT1免疫反应性同时出现在脑室周围白质、前连合和纹状体白质中,在136天时消失。星形胶质细胞内的GLT1蛋白表达受发育调控,60和71天时首先出现在波形蛋白阳性的放射状胶质细胞中,然后在136天时转变为GFAP阳性的实质和血管周围星形胶质细胞。波形蛋白阳性星形胶质细胞亚群中GLT1的表达在白质中持续存在,但在皮质中不存在。这些结果确定了小脑皮质内一种新的分隔以及GLT1在神经元和轴突通路中的定位,表明这种谷氨酸转运体参与了小脑皮质地形组织的发育以及GLT1在发育中的大脑中的短暂神经元功能。此外,GLT1表达具有高度可塑性,在大脑发育过程中既不是仅由星形胶质细胞表达,也不是在不同星形胶质细胞群体中均匀表达。