Alterations in glutamatergic signaling contribute to the decline of circadian photoentrainment in aged mice
Alterations in glutamatergic signaling contribute to the decline of circadian photoentrainment in aged mice
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DOI：
10.1016/j.neurobiolaging.2018.02.013
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发表时间：
2018-06-01
影响因子：
4.2
通讯作者：
Lall, Gurprit S.
中科院分区：
文献类型：
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作者：
Biello, Stephany M.;Bonsall, David R.;Lall, Gurprit S.
强健的生理昼夜节律是健康的一个组成部分。已经发现衰老过程对驱动昼夜生理学的系统产生负面影响，通常表现为与异常/中断的睡眠模式相关的症状。在这里，我们研究了雄性C57 BL/6 J小鼠中光驱动的昼夜节律夹带的年龄相关性下降。我们比较了年轻（1-2个月）和老年（14-18个月）小鼠的昼夜行为活动的光驱动重置，并在昼夜节律起搏器，视交叉上核（SCN）的水平上探索了神经递质通路的改变。老年动物表现出显着降低的敏感性行为阶段重置光。我们表明，这种变化是通过改变N-甲基-D-天冬氨酸（NMDA）信号在SCN，其中NMDA，一种β-amatergic激动剂，是不太有效的诱导时钟重置。最后，我们表明，这种转变在NMDA的敏感性是通过减少SCN的表达，这种受体的NR 2B亚基。只有在年轻的动物NR 2B拮抗剂衰减行为重置。这些结果可以帮助靶向治疗，旨在改善老年人群的生理和行为昼夜节律夹带。(C)2018作者爱思唯尔公司出版
Robust physiological circadian rhythms form an integral part of well-being. The aging process has been found to negatively impact systems that drive circadian physiology, typically manifesting as symptoms associated with abnormal/disrupted sleeping patterns. Here, we investigated the age-related decline in light-driven circadian entrainment in male C57BL/6J mice. We compared light-driven resetting of circadian behavioral activity in young (1-2 months) and old (14-18 months) mice and explored alterations in the glutamatergic pathway at the level of the circadian pacemaker, the suprachiasmatic nucleus (SCN). Aged animals showed a significant reduction in sensitivity to behavioral phase resetting by light. We show that this change was through alterations in N-Methyl-D-aspartate (NMDA) signaling at the SCN, where NMDA, a glutamatergic agonist, was less potent in inducing clock resetting. Finally, we show that this shift in NMDA sensitivity was through the reduced SCN expression of this receptor's NR2B subunit. Only in young animals did an NR2B antagonist attenuate behavioral resetting. These results can help target treatments that aim to improve both physiological and behavioral circadian entrainment in aged populations. (C) 2018 The Authors. Published by Elsevier Inc.