小柯机器人

钠离子可影响生物钟
2020-07-11 13:37

加拿大麦吉尔大学Charles W. Bourque与Claire Gizowski合作发现,钠离子通过兴奋性GABA能途径调控节律时钟。该研究于2020年7月8日在线发表于国际学术期刊《自然》。

研究人员发现,在Zeitgeber期间,即SCNVP(视交叉上核血管加压素)神经元失活的期间,给予全身性盐注射(高渗盐水)会激发SCNVP神经元,并降低无颤动产热(NST)和体温。高渗盐水对NST和体温的影响可通过SCNVP神经元的化学遗传抑制来预防,并通过体内SCNVP神经元的光遗传刺激来模拟。
 
解剖和电生理实验表明,表达谷氨酸脱羧酶(OVLTGAD)的渗透压钠敏感器官血管壁(OVLT)神经元通过γ-氨基丁酸(GABA)的兴奋作用将这些信息传递给SCNVP神经元。OVLTGAD神经元轴突末端的光遗传激活在体外激发了SCNVP神经元,并在体内模拟了高渗盐水对NST和体温的影响。
 
此外,OVLTGAD神经元的化学遗传抑制削弱了全身性高渗盐水对NST和体温的影响。最后,研究人员高渗盐水显著提高了小鼠的昼夜运动能力。OVLTGAD-SCNVP途径的光遗传学激活可以模拟这种效应,而OVLTGAD神经元的化学遗传抑制可以阻止这种效应。
 
总的来说,这些发现表明,节律时钟可以由非光生理因素来调节,并且这些因素可以通过节律输出网络驱动稳态响应。
 
据悉,视交叉上核(SCN)是人体的生物钟,可在整个昼夜周期预期变化的情况下,自适应地协调生理和行为的变化。例如,SCN通过在睡眠前增加水的摄入量,并通过驱动抗利尿激素的分泌和降低体温来减少睡眠期间的水分流失。这些反应也可以由中枢渗透钠传感蛋白驱动,从而抵抗在活动期间渗透压的意外增加。然而,渗透钠传感蛋白是否需要节律输出网络来驱动稳态响应还不清楚。
 
附:英文原文

Title: Sodium regulates clock time and output via an excitatory GABAergic pathway

Author: Claire Gizowski, Charles W. Bourque

Issue&Volume: 2020-07-08

Abstract: The suprachiasmatic nucleus (SCN) serves as the body’s master circadian clock that adaptively coordinates changes in physiology and behaviour in anticipation of changing requirements throughout the 24-h day–night cycle1,2,3,4. For example, the SCN opposes overnight adipsia by driving water intake before sleep5,6, and by driving the secretion of anti-diuretic hormone7,8 and lowering body temperature9,10 to reduce water loss during sleep11. These responses can also be driven by central osmo-sodium sensors to oppose an unscheduled rise in osmolality during the active phase12,13,14,15,16. However, it is unknown whether osmo-sodium sensors require clock-output networks to drive homeostatic responses. Here we show that a systemic salt injection (hypertonic saline) given at Zeitgeber time 19—a time at which SCNVP (vasopressin) neurons are inactive—excited SCNVP neurons and decreased non-shivering thermogenesis (NST) and body temperature. The effects of hypertonic saline on NST and body temperature were prevented by chemogenetic inhibition of SCNVP neurons and mimicked by optogenetic stimulation of SCNVP neurons in vivo. Combined anatomical and electrophysiological experiments revealed that osmo-sodium-sensing organum vasculosum lamina terminalis (OVLT) neurons expressing glutamic acid decarboxylase (OVLTGAD) relay this information to SCNVP neurons via an excitatory effect of γ-aminobutyric acid (GABA). Optogenetic activation of OVLTGAD neuron axon terminals excited SCNVP neurons in vitro and mimicked the effects of hypertonic saline on NST and body temperature in vivo. Furthermore, chemogenetic inhibition of OVLTGAD neurons blunted the effects of systemic hypertonic saline on NST and body temperature. Finally, we show that hypertonic saline significantly phase-advanced the circadian locomotor activity onset of mice. This effect was mimicked by optogenetic activation of the OVLTGAD→ SCNVP pathway and was prevented by chemogenetic inhibition of OVLTGAD neurons. Collectively, our findings provide demonstration that clock time can be regulated by non-photic physiologically relevant cues, and that such cues can drive unscheduled homeostatic responses via clock-output networks.

DOI: 10.1038/s41586-020-2471-x

Source: https://www.nature.com/articles/s41586-020-2471-x

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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