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γ-氨基丁酸转运体GAT1和GAT4的发育性表达表明其参与脑成熟过程。

Developmental expression of GABA transporters GAT1 and GAT4 suggests involvement in brain maturation.

作者信息

Jursky F, Nelson N

机构信息

Roche Institute of Molecular Biology, Roche Research Center, Nutley, New Jersey, USA.

出版信息

J Neurochem. 1996 Aug;67(2):857-67. doi: 10.1046/j.1471-4159.1996.67020857.x.

Abstract

cDNA clones representing four pharmacologically distinct GABA transporters (GAT1-GAT4) were previously identified in mouse brain. Two of these, GAT1 and GAT4, were found to be brain specific. We studied GAT1 and GAT4 in the developing rat brain using polygonal antibodies against recombinant fusion proteins. Patterns of immunoreactivity were very similar in the embryonic and early postnatal stages for both transporters. However, whereas GAT1 immunoreactivity was detected in distinct patterns in gray matter and growing axons, GAT4 immunoreactivity was found in a subset of radial glial cell fascicles. These patterns usually oriented perpendicularly to the axons expressing GAT1. Our results suggest a transient relationship between GAT4-expressing radial glial elements and GAT1-expressing axons. The presence of GAT1 in the cortical marginal zone and the numerous GAT4-positive fascicles observed in the fetal anterior commissure indicate that both transporters may play a role in processes of brain maturation. Because the beginning of expression for both GAT1 and GAT4 correlates with the expression of the alpha1 subunit of the GABA receptor, the transporters may be connected with the maturation of adult-type GABAergic inhibitory system in the brain.

摘要

先前在小鼠大脑中鉴定出代表四种药理学特性不同的γ-氨基丁酸转运体(GAT1 - GAT4)的互补DNA(cDNA)克隆。其中两种,即GAT1和GAT4,被发现具有脑特异性。我们使用针对重组融合蛋白的多克隆抗体,对发育中的大鼠大脑中的GAT1和GAT4进行了研究。在胚胎期和出生后早期阶段,两种转运体的免疫反应模式非常相似。然而,GAT1免疫反应性在灰质和生长中的轴突中以不同模式被检测到,而GAT4免疫反应性则在放射状胶质细胞束的一个子集中被发现。这些模式通常垂直于表达GAT1的轴突。我们的结果表明,表达GAT4的放射状胶质细胞成分与表达GAT1的轴突之间存在短暂的关系。皮质边缘区中GAT1的存在以及在胎儿前连合中观察到的众多GAT4阳性束表明,这两种转运体可能在大脑成熟过程中发挥作用。由于GAT1和GAT4的表达开始与γ-氨基丁酸受体α1亚基的表达相关,这些转运体可能与大脑中成年型γ-氨基丁酸能抑制系统的成熟有关。

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