Differential arousal regulation by prokineticin 2 signaling in the nocturnal mouse and the diurnal monkey.

Differential arousal regulation by prokineticin 2 signaling in the nocturnal mouse and the diurnal monkey.
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DOI:
10.1186/s13041-016-0255-x
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发表时间:
2016-08-18
期刊:
影响因子:
3.6
通讯作者:
Li X
Li X
中科院分区:
医学3区
文献类型:
--
作者:
Zhou QY;Burton KJ;Neal ML;Qiao Y;Kanthasamy AG;Sun Y;Xu X;Ma Y;Li X

文献摘要

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哺乳动物活动/休息或睡眠/觉醒节律的时间组织由光/暗周期和昼夜节律的相互作用调节。对于昼行性和夜行性哺乳动物,将活动期限制在白天或夜晚的神经和分子机制尚不清楚。在这里,我们报告,prokineticin 2,以前显示为生物钟输出分子,在本质上光敏视网膜神经节细胞中表达,和prokineticin 2在本质上光敏视网膜神经节细胞中的表达是振荡的时钟依赖性的方式。我们进一步表明,prokineticin 2信号是必需的活动和唤醒抑制在小鼠中的光。在夜间活动的小鼠和白天活动的猴子之间,在视网膜视交叉上核和上级丘中,内源性光敏视网膜神经节细胞的脑投射靶点中,前动力蛋白2的信号传导受体差异表达。用选择性拮抗剂阻断揭示了前动力蛋白2信号传导对夜间小鼠和昼夜猴的觉醒水平的分别抑制和刺激作用。因此,哺乳动物的昼夜节律性或昼夜节律性可能是由原动力蛋白2从固有光敏视网膜神经节细胞到其视网膜受体脑靶标的差异信号传导决定的。
The temporal organization of activity/rest or sleep/wake rhythms for mammals is regulated by the interaction of light/dark cycle and circadian clocks. The neural and molecular mechanisms that confine the active phase to either day or night period for the diurnal and the nocturnal mammals are unclear. Here we report that prokineticin 2, previously shown as a circadian clock output molecule, is expressed in the intrinsically photosensitive retinal ganglion cells, and the expression of prokineticin 2 in the intrinsically photosensitive retinal ganglion cells is oscillatory in a clock-dependent manner. We further show that the prokineticin 2 signaling is required for the activity and arousal suppression by light in the mouse. Between the nocturnal mouse and the diurnal monkey, a signaling receptor for prokineticin 2 is differentially expressed in the retinorecipient suprachiasmatic nucleus and the superior colliculus, brain projection targets of the intrinsically photosensitive retinal ganglion cells. Blockade with a selective antagonist reveals the respectively inhibitory and stimulatory effect of prokineticin 2 signaling on the arousal levels for the nocturnal mouse and the diurnal monkey. Thus, the mammalian diurnality or nocturnality is likely determined by the differential signaling of prokineticin 2 from the intrinsically photosensitive retinal ganglion cells onto their retinorecipient brain targets.