Expression of alpha2A adrenoceptors during rat neocortical development.

Expression of alpha2A adrenoceptors during rat neocortical development.
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DOI:
10.1002/(sici)1097-4695(19990205)38:2
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发表时间:
1999-02
期刊:
Journal of neurobiology
影响因子:
--
通讯作者:
U. Winzer-Serhan;F. Leslie
U. Winzer-Serhan;F. Leslie
中科院分区:
其他
文献类型:
--
作者:
U. Winzer-Serhan;F. Leslie

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去甲肾上腺素被认为在发育过程中发挥神经营养作用,早在胚胎第12天(E)就存在于大脑中。我们最近已经证明,α 2A肾上腺素受体亚型广泛表达的神经元迁移和分化的整个发育中的大脑的时间。在这里,我们报告的时间和空间表达模式的α 2A肾上腺素受体在新皮层在胚胎晚期和出生后早期的发展,使用原位杂交和受体放射自显影。还使用激动剂刺激的[35S] GTP γ S放射自显影术检测胚胎大鼠皮质中的功能性α 2受体。E19和E20分别强烈增加了α 2A mRNA和蛋白表达。皮质板、中间区和室管膜下区表达增加,与迁移和分化的神经元层相对应。这种短暂的α 2A肾上腺素受体上调仅限于外侧新皮质。在E20,功能性α 2肾上腺素受体也检测到在深层的外侧新皮层。在出生后发育的第一周,α 2A mRNA和蛋白质的表达发生了显着变化,引起了更成熟的解剖分布模式。在发育中的新皮层中α 2A肾上腺素受体的时空分布与迁移和分化的IV层至II层神经元上的功能蛋白的表达一致。这些发现表明,α 2A受体可能介导的去甲肾上腺素在胎儿皮质发育的神经营养作用。外侧新皮层的早期描绘,这将发展成体感和听觉皮层,表明α 2A mRNA表达的内在调节。
Norepinephrine has been suggested to play a neurotrophic role during development and is present in the brain as early as embryonic day (E) 12. We have recently demonstrated that the alpha2A adrenoceptor subtype is widely expressed during times of neuronal migration and differentiation throughout the developing brain. Here, we report the temporal and spatial expression pattern of alpha2A adrenoceptors in neocortex during late embryonic and early postnatal development using in situ hybridization and receptor autoradiography. Functional alpha2 receptors in embryonic rat cortex were also detected using agonist stimulated [35S]GTPgammaS autoradiography. Both alpha2A mRNA and protein expression were strongly increased by E19 and E20, respectively. The increased expression was in the cortical plate and intermediate and subventricular zones, corresponding to tiers of migrating and differentiating neurons. This transient up-regulation of alpha2A adrenoceptors was restricted to the lateral neocortex. At E20, functional alpha2 adrenoceptors were also detected in deep layers of lateral neocortex. During the first week of postnatal development, the expression of alpha2A mRNA and protein changed markedly, giving rise to a more mature pattern of anatomical distribution. The temporal and spatial distribution of alpha2A adrenoceptors in developing neocortex is consistent with expression of functional proteins on migrating and differentiating layer IV to II neurons. These findings suggest that alpha2A receptors may mediate a neurotrophic effect of norepinephrine during fetal cortical development. The early delineation of the lateral neocortex, which will develop into somatosensory and auditory cortices, suggests an intrinsic regulation of alpha2A mRNA expression.