Characterization of sevoflurane effects on Per2 expression using ex vivo bioluminescence imaging of the suprachiasmatic nucleus in transgenic rats
Characterization of sevoflurane effects on Per2 expression using ex vivo bioluminescence imaging of the suprachiasmatic nucleus in transgenic rats
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DOI：
10.1016/j.neures.2015.11.010
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发表时间：
2016-06-01
影响因子：
2.9
通讯作者：
Ozawa, Hitoshi
中科院分区：
文献类型：
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作者：
Matsuo, Izumi;Iijima, Norio;Ozawa, Hitoshi
吸入麻醉剂七氟烷抑制啮齿动物视交叉上核（SCN）中的Per 2表达。在这里，我们研究了七氟醚作用的SCN内区域特异性、时间依赖性和药理学基础。从mPer 2启动子去稳定化的荧光素酶转基因大鼠的SCN外植体拍摄生物发光图像，并分析图像的每个小的感兴趣区域（ROI）。七氟烷抑制所有ROI中的生物发光，表明SCN中的所有区域对七氟烷敏感。还观察到七氟烷效应具有明显的时间依赖性;在生物发光周期的谷期应用七氟烷抑制了随后的生物发光增加，并导致周期的相位延迟;在上升期中期应用七氟烷诱导了相位提前;在下降期应用七氟烷未显示任何影响。这些结果表明，七氟烷的作用可能取决于昼夜节律机制的内在状态。最后，我们研究了七氟烷效应中GABA能信号转导的参与。GABA（A）和GABA（B）受体拮抗剂的联合应用完全阻断了七氟烷对生物发光节律的影响，表明七氟烷通过GABA能信号转导抑制Per 2表达。目前的研究阐明了麻醉对昼夜节律的分子机制的影响。(C)2015 Elsevier爱尔兰有限公司和日本神经科学学会。All rights reserved.
The inhalation anesthetic sevoflurane suppresses Per2 expression in the suprachiasmatic nucleus (SCN) in rodents. Here, we investigated the intra-SCN regional specificity, time-dependency, and pharmacological basis of sevoflurane-effects. Bioluminescence image was taken from the SCN explants of mPer2 promoter-destabilized luciferase transgenic rats, and each small regions of interest (ROI) of the image was analyzed. Sevoflurane suppressed bioluminescence in all ROIs, suggesting that all regions in the SCN are sensitive to sevoflurane. Clear time-dependency in sevoflurane effects were also observed; application during the trough phase of the bioluminescence cycle suppressed the subsequent increase in bioluminescence and resulted in a phase delay of the cycle; sevoflurane applied during the middle of the ascending phase induced a phase advance; sevoflurane on the descending phase showed no effect. These results indicate that the sevoflurane effect may depend on the intrinsic state of circadian machinery. Finally, we examined the involvement of GABAergic signal transduction in the sevoflurane effect. Co-application of both GABA(A) and GABA(B) receptor antagonists completely blocked the effect of sevoflurane on the bioluminescence rhythm, suggesting that sevoflurane inhibits Per2 expression via GABAergic signal transduction. Current study elucidated the anesthetic effects on the molecular mechanisms of circadian rhythm. (C) 2015 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.