Mice Genetically Deficient in Vasopressin V1a and V1b Receptors Are Resistant to Jet Lag
Mice Genetically Deficient in Vasopressin V1a and V1b Receptors Are Resistant to Jet Lag
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DOI：
10.1126/science.1238599
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发表时间：
2013-10-04
期刊：
影响因子：
56.9
通讯作者：
Okamura, Hitoshi
中科院分区：
文献类型：
--
作者：
Yamaguchi, Yoshiaki;Suzuki, Toru;Okamura, Hitoshi
时差综合征是由于体内生物钟和外部太阳时之间的时间错位引起的。我们发现，在缺乏加压素受体V1 a和V1 b（V1 a（-/-）V1 b（-/-））的小鼠中，行为（运动活动）、时钟基因表达和体温的昼夜节律立即重新进入相移的明暗周期。尽管如此，V1 a（-/-）V1 b（-/-）小鼠的行为仍然与内部时钟相关联，该时钟在标准条件下正常振荡。在培养中的视交叉上核（SCN）切片的实验表明，由V1 a和V1 b介导的神经元间的通信赋予SCN对外部扰动的内在抵抗力。野生型小鼠SCN中V1 a和V1 b的药理学阻断导致加速从时差中恢复，这突出了加压素信号传导作为昼夜节律失调管理的治疗靶点的潜力，例如时差和轮班工作。
Jet-lag symptoms arise from temporal misalignment between the internal circadian clock and external solar time. We found that circadian rhythms of behavior (locomotor activity), clock gene expression, and body temperature immediately reentrained to phase-shifted light-dark cycles in mice lacking vasopressin receptors V1a and V1b (V1a(-/-)V1b(-/-)). Nevertheless, the behavior of V1a(-/-)V1b(-/-) mice was still coupled to the internal clock, which oscillated normally under standard conditions. Experiments with suprachiasmatic nucleus (SCN) slices in culture suggested that interneuronal communication mediated by V1a and V1b confers on the SCN an intrinsic resistance to external perturbation. Pharmacological blockade of V1a and V1b in the SCN of wild-type mice resulted in accelerated recovery from jet lag, which highlights the potential of vasopressin signaling as a therapeutic target for management of circadian rhythm misalignment, such as jet lag and shift work.