Independent maturation of the GABAB receptor subunits GABAB1 and GABAB2 during postnatal development in rodent brain
Independent maturation of the GABAB receptor subunits GABAB1 and GABAB2 during postnatal development in rodent brain
复制标题
DOI：
10.1002/cne.20188
复制
发表时间：
2004-09-20
影响因子：
2.5
通讯作者：
Benke, D
中科院分区：
文献类型：
--
作者：
Fritschy, JM;Sidler, C;Benke, D
GABA（B）受体介导缓慢的抑制性GABA能神经传递。它们由两个不同的亚基GABA（B1）编码。（GBR 1）和GABA（B2）（GBR 2），具有GBR 1的两种主要同种型，GBR 1a和GBR 1b，由差异启动子使用引起。如重组表达系统和GBR 1（-/-）小鼠中所示，GBR 1和GBR 2的异源二聚化对于GABA（B）受体功能是必需的。GABA（B）受体在突触发生之前的个体发育过程中高度表达，但其发育功能仍不清楚。在这里，我们调查了出生后的发育GABA（B）受体在啮齿动物的大脑，集中在GBR 1和GBR 2的时空表达模式的潜在差异。亚单位特异性抗体的免疫组织化学显示，新生啮齿动物脑中GBR 1a和GBR 2广泛染色。在前2周，这两个亚基表现出很大程度上重叠的区域分布，但在细胞和亚细胞定位的深刻区别。在第三周期间建立了成人样模式，GBR 1b显著上调，与GBR 2广泛共分布。在早期阶段注意到几个意想不到的特征，特别是轴突束的选择性GBR 2染色，如皮质丘脑投射，以及星形胶质细胞中的显著GBR 1表达。在GBR 1和GBR 2基因敲除小鼠中验证了抗体标记的特异性。此外，对这些突变体的分析揭示了GBR 1（-/-）小鼠中GBR 2染色的部分保留，反之亦然。总之，结果表明，GBR 1和GBR 2蛋白在未成熟的大脑中的功能作用，除了他们的贡献二聚体GABA（B）受体复合物。(C)2004 Wiley-Liss，Inc.
GABA(B) receptors mediate slow inhibitory GABAergic neurotransmission. They are encoded by two distinct subunits, GABA(B1). (GBR1) and GABA(B2) (GBR2), with two major isoforms of GBR1, GBR1a and GBR1b, arising from differential promoter usage. Heterodimerization of GBR1 and GBR2 is essential for GABA(B) receptor function, as shown in recombinant expression systems and in GBR1(-/-) mice. GABA(B) receptors are highly expressed during ontogeny, prior to synaptogenesis, but their developmental function remains elusive. Here we investigated the postnatal development of GABA(B) receptors in rodent brain, focusing on potential differences in the spatial and temporal expression pattern of GBR1 and GBR2. Immunohistochemistry with subunit-specific antibodies revealed a widespread staining for GBR1a and GBR2 in neonatal rodent brain. During the first 2 weeks, these two subunits exhibited largely overlapping regional distribution, but with profound distinctions in cellular and subcellular localization. The adult-like pattern was established during the third week, with a prominent up-regulation of GBR1b, extensively codistributed with GBR2. Several unexpected features were noted at early stages, notably, a selective GBR2 staining of axonal tracts, such as the corticothalamic projection, and a prominent GBR1 expression in astrocytes. The specificity of the antibody labeling was verified in GBR1- and GBR2-knockout mice. In addition, the analysis of these mutants revealed a partial preservation of GBR2 staining in GBR1(-/-) mice and vice versa. Altogether, the results suggest a functional role for GBR1 and GBR2 proteins in immature brain in addition to their contribution to dimeric GABA(B) receptor complexes. (C) 2004 Wiley-Liss, Inc.