Winzer-Serhan U H, Raymon H K, Broide R S, Chen Y, Leslie F M
Department of Pharmacology, College of Medicine, University of California, Irvine 92717, USA.
Neuroscience. 1997 Jan;76(1):241-60. doi: 10.1016/s0306-4522(96)00368-5.
The distribution of alpha 2A adrenoceptor messenger RNA expression in developing rat brain was characterized using in situ hybridization with 35S-labeled riboprobes. Intense hybridization signal was detected as early as embryonic day 14 in several areas adjacent to the forebrain and hindbrain germinal zones and in central noradrenergic neurons. A marked increase in messenger RNA expression was observed throughout the brain during late prenatal development, consistent with the migration and maturation of neurons in developing brain structures. In embryonic brain, there was a temporal and spatial correspondence in the appearance of alpha 2A messenger RNA expression and binding sites labeled with [3H]idazoxan or p-[125I]iodoclonidine, indicating translation into receptor protein at an early stage of development. Whereas the presynaptic expression remained constant throughout development, there was an early postnatal decline of alpha 2A receptor expression in many brain regions, including the olfactory bulb, cortex, caudate-putamen, hippocampus, thalamus, hypothalamus and medulla. Thereafter, messenger RNA expression increased, establishing an adult-like pattern during the second postnatal week, but remained low in areas such as the caudate-putamen, thalamus and hippocampus, which do not exhibit extensive expression in the adult. The transient perinatal expression of this alpha 2 adrenoceptor type, which coincides with a period of hyperreactivity to sensory stimuli in the locus coeruleus, may indicate a specific functional role for the alpha 2A receptor in the developing rat brain. The early and intense expression in olfactory structures suggests an involvement in early olfactory learning. The pattern of widespread, transient expression of alpha 2A receptors in the fetal brain is in marked contrast to the postnatal development of the alpha 2C receptor type.
利用与35S标记的核糖探针进行原位杂交，对发育中大鼠脑内α2A肾上腺素能受体信使核糖核酸（mRNA）的表达分布进行了特征描述。早在胚胎第14天，在前脑和后脑生发区附近的几个区域以及中枢去甲肾上腺素能神经元中就检测到了强烈的杂交信号。在产前发育后期，整个大脑中观察到信使核糖核酸表达显著增加，这与发育中脑结构中神经元的迁移和成熟一致。在胚胎脑中，α2A信使核糖核酸表达的出现与用[3H]咪唑克生或对-[125I]碘氯苯胍标记的结合位点在时间和空间上相对应，表明在发育早期就翻译成了受体蛋白。虽然突触前表达在整个发育过程中保持恒定，但在许多脑区，包括嗅球、皮质、尾状核-壳核、海马、丘脑、下丘脑和延髓，α2A受体表达在出生后早期有所下降。此后，信使核糖核酸表达增加，在出生后第二周建立起类似成年的模式，但在尾状核-壳核、丘脑和海马等区域仍保持低水平，这些区域在成年期不表现出广泛表达。这种α2肾上腺素能受体亚型在围产期的短暂表达，与蓝斑对感觉刺激的高反应期相吻合，可能表明α2A受体在发育中的大鼠脑中具有特定的功能作用。在嗅觉结构中的早期和强烈表达表明其参与早期嗅觉学习。α2A受体在胎儿脑中广泛、短暂表达的模式与α2C受体亚型的出生后发育形成显著对比。
