Development of the norepinephrine transporter in the rat CNS.
Development of the norepinephrine transporter in the rat CNS.
复制标题
大鼠中枢神经系统去甲肾上腺素转运蛋白的发育。
DOI：
10.1016/j.neuroscience.2004.09.014
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Murrin,LC
中科院分区：
文献类型：
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作者：
Sanders,JD;Happe,HK;Bylund,DB;Murrin,LC
去甲肾上腺素转运体(Net)通过将去甲肾上腺素从突触中移除，在调节去甲肾上腺素的作用中起着重要作用。许多研究表明，去甲肾上腺素在调节中枢神经系统的发育中起着重要作用，并指出去甲肾上腺素是这一过程中的一个重要因素。以[~3H]尼索西汀为配基，用放射自显影技术研究了出生后5、10、15、20、25天(PND)大鼠和成年大鼠脑内Net表达的个体发育。在PND 5和10，大多数前脑区有低净表达(1-2fmol/mg组织)。到了PND 15，大多数前脑区域的净表达增加了大约5倍，与PND 10相比，水平大致与成人大脑中发现的水平相似。相反，脑干的净发育在PND 5、10和20时密度增加，而成年后密度降低。特别是蓝斑，在出生后早期有非常高的净表达，但在成年大脑中显著减少。这些数据显示了Net的动态个体发育概况，其特征是前脑结构的发育性增加和脑干的相反减少。Net在出生后早期在脑干中的表达，以及随后随着成熟期Net表达的减少或丧失，表明该转运蛋白和去甲肾上腺素在许多脑区的发育中起着重要的作用。这些研究对儿童和青少年使用针对去甲肾上腺素系统的药物也有重要意义，例如抗抑郁药和滥用药物。
The norepinephrine transporter (NET) plays a major role in regulating the actions of norepinephrine by removing norepinephrine from the synapse. Many studies suggest norepinephrine plays an important role in regulating development of the CNS, pointing to NET as an important factor in this process. We examined the ontogeny of NET expression in rat brain at 5, 10, 15, 20 and 25 days postnatally (PND) and in adults, using quantitative autoradiography with [3H]nisoxetine as ligand. At PND 5 and 10 most forebrain areas had low NET expression (1–2 fmol/mg tissue). By PND 15 most forebrain areas increased NET expression approximately five-fold compared with PND 10, levels generally similar to those found in the adult brain. In contrast, NET development in the brainstem exhibited elevated densities at PND 5, 10 and 20 that decreased in the adult. The locus coeruleus, in particular, had very high NET expression in the early postnatal period that decreased dramatically in the adult brain. These data illustrate a dynamic ontogenic profile for NET, characterized by developmental increases in forebrain structures and contrasting decreases in the brainstem. The early postnatal expression of NET in brainstem and the subsequent decrease or loss of NET expression with maturation suggest an important role for this transporter and for norepinephrine in the development of many brain regions. These studies also have important implications for use of drugs targeting the noradrenergic system in children and adolescents, such as antidepressants and drugs of abuse.