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大鼠下丘脑视上核中NR1和NR2B亚基表达的发育可塑性。

Developmental plasticity of NR1 and NR2B subunit expression in the supraoptic nucleus of the rat hypothalamus.

作者信息

Currás M C, Dao J

机构信息

Department of Neuroscience, University of California at Riverside 92521, USA.

出版信息

Brain Res Dev Brain Res. 1998 Jul 1;109(1):1-12. doi: 10.1016/s0165-3806(98)00060-1.

Abstract

Vasopressin and oxytocin neuroendocrine cells within the supraoptic nucleus of the adult hypothalamus (SON) display mRNA expression for the NMDA receptor subunits, NR1 and NR2B, NR2C and NR2D. The NR2B subunit confers slow decay kinetics (relative to NR1/NR2A receptors) and high magnesium sensitivity to NMDA receptor responses--properties which may contribute to the NMDA receptor-mediated bursting manifested by these cells. Therefore, we examined NR2B protein expression and its developmental profile in the SON and compared it to that in the cortex and cerebellum--areas which have been studied previously. We performed Western blot analysis on SON homogenates from embryonic, postnatal (PN7, 14, 21), and adult rats using an NR2B-specific antibody. Adult NR2B levels in the SON and PVN were similar but low relative to those of cortex. SON NR2B protein levels rose in the first postnatal week, remained high through PN21, and later declined to significantly lower levels in the adult. A similar profile was observed in cerebellum, where NR2B expression displayed a sharp peak at PN14 and later declined to minimal or undetectable levels in the adult. In contrast, NR2B continued to be overexpressed through adulthood in the cortex. The ontogenic pattern for NR1 expression, which included unregulation during early postnatal life and adulthood, was similar in the SON and cortex. A different pattern was observed for the cerebellum, where NR1 levels increased gradually after ED17 to reach significantly greater adult levels. Of all three areas studied, the SON displayed the earliest developmental rise in NR1 levels. SON explant cultures proved to be a useful preparation, since they contained neurons which synthesized NR1 and NR2B subunits in quantities similar to those of ED17 SON. Our findings suggest that NMDA receptors on SON neuroendocrine cells are assembled using NR1 and NR2B subunits, and that their plastic expression in early postnatal life may play a role during development.

摘要

成年下丘脑视上核(SON)内的血管加压素和催产素神经内分泌细胞表达NMDA受体亚基NR1、NR2B、NR2C和NR2D的mRNA。相对于NR1/NR2A受体,NR2B亚基赋予NMDA受体反应缓慢的衰减动力学和高镁敏感性,这些特性可能有助于这些细胞表现出的NMDA受体介导的爆发性放电。因此,我们检测了SON中NR2B蛋白的表达及其发育情况,并将其与之前研究过的皮质和小脑区域进行比较。我们使用NR2B特异性抗体对胚胎期、出生后(PN7、14、21)和成年大鼠的SON匀浆进行了蛋白质免疫印迹分析。SON和室旁核(PVN)中成年NR2B水平相似,但相对于皮质较低。SON中NR2B蛋白水平在出生后第一周上升,在PN21时保持较高水平,随后在成年期降至显著较低水平。在小脑中观察到类似的情况,其中NR2B表达在PN14时出现尖峰,随后在成年期降至最低或不可检测水平。相比之下,NR2B在成年期的皮质中持续过度表达。NR1表达的个体发育模式,包括在出生后早期和成年期的上调,在SON和皮质中相似。在小脑中观察到不同的模式,其中NR1水平在胚胎期第17天(ED17)后逐渐增加,在成年期达到显著更高水平。在所有研究的三个区域中,SON显示出NR1水平最早的发育性上升。SON外植体培养被证明是一种有用的制备方法,因为它们包含的神经元合成NR1和NR2B亚基的量与ED17的SON相似。我们的研究结果表明,SON神经内分泌细胞上的NMDA受体是由NR1和NR2B亚基组装而成的,并且它们在出生后早期的可塑性表达可能在发育过程中发挥作用。

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