Circadian variation of metabotropic glutamate receptor 5 availability in the rat brain
Circadian variation of metabotropic glutamate receptor 5 availability in the rat brain
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DOI：
10.1111/jsr.12432
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发表时间：
2016-12-01
影响因子：
4.4
通讯作者：
Bauer, Andreas
中科院分区：
文献类型：
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作者：
Elmenhorst, David;Mertens, Kristina;Bauer, Andreas
代谢型谷氨酸受体(MGluR5)除了与抑郁症等多种神经系统疾病有关外，还在突触可塑性中发挥重要作用。由于mGluR5在人类中的可用性在睡眠剥夺中发生改变，我们假设mGluR5的可用性是昼夜节律变化的基础。为了研究mGluR5是否是潜在的昼夜节律变化的基础，我们在11只成年SD大鼠的六个不同的白天以随机的方式测量了它的密度。MGluR5密度用放射性配体[C-11]ABP688的正电子发射断层扫描(PET)进行定量。[C-11]使用参考组织模型对9个感兴趣区域的ABP688摄取进行了量化。大脑皮层、扣带回、杏仁核、尾壳核和伏核的结合电位(BPND)和mGluR5利用率在不同昼夜之间存在显著差异。对不同时间点的进一步统计分析(Tukey-Kramer检验)显示，尾壳核BPND在07：00小时(点亮阶段开始)至15：00小时(点亮阶段的最后时间点)之间有显著变化。这项研究表明，在啮齿动物的开机或睡眠阶段，mGluR5的利用率增加了约10%。鉴于mGluR5密度的改变在精神障碍中发挥作用，有必要进行进一步的研究，以评估它们与人类情绪变化的昼夜节律有关。
The metabotrophic subtype 5 glutamate receptor (mGluR5) plays a critical role in synaptic plasticity besides its involvement in numerous neurological disorders, such as depression. As mGluR5 availability in humans is altered in sleep deprivation, we hypothesized that mGluR5 availability underlies a circadian variation. To investigate whether mGluR5 underlies potential circadian changes we measured its density in a randomized fashion at six different daytimes in 11 adult Sprague-Dawley rats. mGluR5 density was quantified by positron emission tomography (PET) using the radioactive ligand [C-11] ABP688. [C-11] ABP688 uptake was quantified in nine regions of interest with a reference tissue model. Significant differences in the binding potential (BPND) and therefore mGluR5 availability between the different circadian times were found in cortex, cingulate cortex, amygdala, caudate putamen and nucleus accumbens. Further post-hoc statistical analysis (Tukey-Kramer test) of the different time-points revealed significant changes in BPND between 07: 00 hours (start of light-on phase) and 15: 00 hours (last time-point of the light-on phase) in the caudate putamen. This study shows that mGluR5 availability is increased during the light-on, or sleep phase, of rodents by approximately 10%. Given that altered mGluR5 densities play a role in psychiatric disorders, further investigation is warranted to evaluate their circadian involvement in mood changes in humans.