DEVELOPMENTAL EXPRESSION OF THE GABA-A RECEPTOR ALPHA-1 SUBUNIT MESSENGER-RNA IN THE RAT-BRAIN
DEVELOPMENTAL EXPRESSION OF THE GABA-A RECEPTOR ALPHA-1 SUBUNIT MESSENGER-RNA IN THE RAT-BRAIN
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DOI：
10.1002/neu.480210803
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发表时间：
1990-12-01
期刊：
影响因子：
--
通讯作者：
SIEGEL, RE
中科院分区：
文献类型：
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作者：
GAMBARANA, C;PITTMAN, R;SIEGEL, RE
最近的研究表明，GABAA，受体复合物，抑制性神经递质γ氨基丁酸（GABAA）和抗焦虑苯二氮卓类药物的作用部位，是异质性的。此外，其组成在发育过程中可能会发生变化。为了更好地理解受体异质性的分子基础，用定量原位杂交组织化学检查了发育和成年大鼠脑中编码α 1受体亚基的mRNA的水平和分布。我们的研究表明，α 1亚基mRNA表达在个体发育过程中发生变化。在胚胎晚期和出生后第一周，在皮质、下丘和海马中检测到低水平的mRNA。这些区域的mRNA水平在出生后第二和第三周增加。此外，在出生后第二周，当信息首次在小脑皮层中变得可检测时，观察到α 1亚基mRNA分布的显著变化。在随后的发育过程中和在成熟脑中，α 1亚基mRNA在小脑、嗅球和下丘中最丰富，尽管mRNA的绝对水平在选定的脑区域中变化多达六倍。α 1亚基mRNA的成熟分布，连同其在小脑中的暂时出现，表明该亚基是GABAA受体复合物的1型苯并二氮杂位点的组分。此外，小脑皮质中α 1亚基mRNA表达的开始与广泛的突触形成的时期相一致，提高了突触相互作用调节小脑中该GABAA受体亚基的出现的可能性。
Recent studies have suggested that the GABAA, receptor complex, the site of action of the inhibitory neurotransmitter gamma amino-butyric acid (GABAA) and the anxiolytic benzodiazepines, is heterogeneous. Moreover, its composition may change during development. To better understand the molecular basis of receptor heterogeneity, the levels and distribution of the mRNA encoding the .alpha.1 receptor subunit were examined in the developing and adult rat brain with quantitative in situ hybridization histochemistry. Our studies demonstrate that .alpha.1 subunit mRNA expression changes during ontogeny. At late embryonic stages and in the first postnatal week, low levels of the mRNA were detected in the cortex, inferior colliculus, and hippocampus. The mRNA levels in these regions increased during the second and third postnatal weeks. Furthermore, a dramatic change in the distribution of the .alpha.1 subunit mRNA was seen in the second postnatal week when the message first became detectable in the cerebellar cortex. During subsequent development and in the mature brain, the .alpha.1 subunit mRNA was most abundant in the cerebellum, olfactory bulb, and inferior colliculus, although the absolute levels of mRNA varied by as much as sixfold in selected brain regions. The mature distribution of .alpha.1 subunit mRNA, alone with its temporal appearance in the cerebellum, suggests that this subunit is a constituent of the Type 1 benzodiazepine site of the GABAA receptor complex. Furthermore, the onset of .alpha.1 subunit mRNA expression in the cerebellar cortex coincides with a period of extensive synapse formation, raising the possibility that synaptic interactions modulate the appearance of this GABAA receptor subunit in the cerebellum.