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首页> 外文期刊>The European Journal of Neuroscience >Role for the NR2B subunit of the N-methyl-D-aspartate receptor in mediating light input to the circadian system.
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Role for the NR2B subunit of the N-methyl-D-aspartate receptor in mediating light input to the circadian system.

机译：N-甲基-D-天冬氨酸受体的NR2B亚基在介导输入到昼夜节律系统的光中的作用。

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摘要

Light information reaches the suprachiasmatic nucleus (SCN) through a subpopulation of retinal ganglion cells that utilize glutamate as a neurotransmitter. A variety of evidence suggests that the release of glutamate then activates N-methyl-D-aspartate (NMDA) receptors within the SCN and triggers a signaling cascade that ultimately leads to phase shifts in the circadian system. In this study, we first sought to explore the role of the NR2B subunit in mediating the effects of light on the circadian system of hamsters and mice. We found that localized microinjection of the NR2B subunit antagonist ifenprodil into the SCN region reduces the magnitude of light-induced phase shifts of the circadian rhythm in wheel-running activity. Next, we found that the NR2B message and levels of phospho-NR2B vary with time of day in SCN tissue using semiquantitative real-time polymerase chain reaction and western blot analysis, respectively. Functionally, we found that blocking the NR2B subunit with ifenprodil significantly reduced the magnitude of NMDA currents recorded in SCN neurons. Ifenprodil also significantly reduced the magnitude of NMDA-induced Ca2+ changes in SCN cells. Together, these results demonstrate that the NR2B subunit is an important component of NMDA receptor-mediated responses within SCN neurons and that this subunit contributes to light-induced phase shifts of the mammalian circadian system.
机译：光信息通过利用谷氨酸盐作为神经递质的视网膜神经节细胞亚群到达视交叉上核（SCN）。各种各样的证据表明，谷氨酸的释放会激活SCN中的N-甲基-D-天冬氨酸（NMDA）受体，并触发信号级联，最终导致昼夜节律系统发生相移。在这项研究中，我们首先试图探索NR2B亚基在介导光对仓鼠和小鼠的昼夜节律系统的影响中的作用。我们发现NR2B亚基拮抗剂ifenprodil的局部显微注射进入SCN区域可降低轮转活动中昼夜节律的光诱导相移的大小。接下来，我们使用半定量实时聚合酶链反应和蛋白质印迹分析分别发现了SCN组织中的NR2B信息和磷酸化NR2B的水平随一天的时间而变化。在功能上，我们发现用艾芬地洛尼阻断NR2B亚基可显着降低SCN神经元中记录的NMDA电流的大小。 Ifenprodil还可以显着降低NMDA诱导SCN细胞中Ca2 +变化的程度。总之，这些结果表明，NR2B亚基是N​​MDA受体介导的SCN神经元内反应的重要组成部分，并且该亚基有助于哺乳动物昼夜节律系统的光诱导相移。

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