Marquette University, Department of Biomedical Sciences, United States of America.
Marquette University, Department of Biomedical Sciences, United States of America.
Horm Behav. 2021 Jan;127:104888. doi: 10.1016/j.yhbeh.2020.104888. Epub 2020 Dec 14.
Arginine vasopressin (AVP) is a neurohormone that alters cellular physiology through both endocrine and synaptic signaling. Circadian rhythms in AVP release and other biological processes are driven by the suprachiasmatic nucleus (SCN) of the anterior hypothalamus. Loss of vasopressin signaling alters circadian behavior, but the basis of these effects remains unclear. Here we investigate the role of AVP signaling in circadian timekeeping by analyzing behavior and SCN function in a novel AVP-deficient mouse model. Consistent with previous work, loss of AVP signaling increases water consumption and accelerates recovery to simulated jetlag. We expand on these results to show that loss of AVP increases period, imprecision and plasticity of behavioral rhythms under constant darkness. Interestingly, the effect of AVP deficiency on circadian period was influenced by sex, with loss of AVP lengthening period in females but not males. Examining SCN function directly with ex vivo bioluminescence imaging of clock protein expression, we demonstrate that loss of AVP signaling modulates the period, precision, and phase relationships of SCN neurons in both sexes. This pattern of results suggests that there are likely sex differences in downstream targets of the SCN. Collectively, this work indicates that AVP signaling modulates circadian circuits in a manner influenced by sex, which provides new insight into sexual dimorphisms in the regulation of daily rhythms.
精氨酸加压素（AVP）是一种神经激素，通过内分泌和突触信号来改变细胞生理学。AVP 释放和其他生物过程的昼夜节律由下丘脑前部的视交叉上核（SCN）驱动。血管加压素信号的丧失改变了昼夜节律行为，但这些影响的基础仍不清楚。在这里，我们通过分析新型 AVP 缺陷小鼠模型中的行为和 SCN 功能，研究了 AVP 信号在昼夜计时中的作用。与以前的工作一致，AVP 信号的丧失增加了水的消耗，并加速了模拟时差的恢复。我们扩展了这些结果，表明 AVP 缺乏会增加行为节律的周期、不准确性和可塑性在持续黑暗下。有趣的是，AVP 缺乏对昼夜节律周期的影响受到性别的影响，AVP 的丧失使雌性的周期延长，但对雄性没有影响。通过对生物钟蛋白表达的离体生物发光成像直接研究 SCN 功能，我们证明 AVP 信号的丧失调节了两性 SCN 神经元的周期、精度和相位关系。这种结果模式表明，SCN 的下游靶标可能存在性别差异。总的来说，这项工作表明，AVP 信号以受性别影响的方式调节昼夜节律回路，这为日常节律调节中的性别二态性提供了新的见解。
