Thermoregulatory phenotype of the Trpv1 knockout mouse: thermoeffector dysbalance with hyperkinesis.
Thermoregulatory phenotype of the Trpv1 knockout mouse: thermoeffector dysbalance with hyperkinesis.
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DOI：
10.1523/jneurosci.4671-10.2011
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发表时间：
2011-02-02
期刊：
影响因子：
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通讯作者：
Romanovsky AA
中科院分区：
文献类型：
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作者：
Garami A;Pakai E;Oliveira DL;Steiner AA;Wanner SP;Almeida MC;Lesnikov VA;Gavva NR;Romanovsky AA
本研究旨在确定缺乏瞬时受体电位香草酸-1(TRPV1)通道的小鼠的体温调节表型。我们使用TRPV1基因敲除(KO)小鼠和它们的遗传未改变的后代来研究基础条件下深部体温(TB)和温度效应器活动的日变化，以及对严热和严寒的体温调节反应。在TRPV1 KO小鼠的基础结核病或它们对热挑战的结核病反应中，只发现了细微的变化。TRPV1KO小鼠的主要体温调节异常是用于调节TB的不同模式的热效应器。在自主神经方面，TRPV1 KO小鼠代谢不足(耗氧量较低)，血管收缩(尾部皮肤温度较低)。与增强的皮肤血管收缩一致，TRPV1 KO小鼠有更高的温度中性区。在行为方面，TRPV1 KO小鼠喜欢较低的环境温度，并表现出较高的运动活动。用药物TRPV1激动剂(resiniferatoxin和anandide)和TRPV1拮抗剂(AMG0347)进行的实验证实，位于大脑外部的TRPV1通道可以强直地抑制运动活动。随着年龄的增长(观察长达14个月)，TRPV1 KO小鼠的体质量超过对照组，有时接近60g。综上所述，TRPV1 KO小鼠具有独特的体温调节表型，与年龄相关的超重的易感性相结合，包括代谢不足、皮肤血管收缩增强、热公投减少和运动亢进。后者可能是TRPV1 KO小鼠的主要缺陷之一。我们认为，TRPV1介导的来自外周的信号调谐地抑制了一般的运动活动。
This study aimed at determining the thermoregulatory phenotype of mice lacking transient receptor potential vanilloid-1 (TRPV1) channels. We used Trpv1 knockout (KO) mice and their genetically unaltered littermates to study diurnal variations in deep body temperature (Tb) and thermoeffector activities under basal conditions, as well as thermoregulatory responses to severe heat and cold. Only subtle alterations were found in the basal Tb of Trpv1 KO mice or in their Tb responses to thermal challenges. The main thermoregulatory abnormality of Trpv1 KO mice was a different pattern of thermoeffectors used to regulate Tb. On the autonomic side, Trpv1 KO mice were hypometabolic (had a lower oxygen consumption) and hypervasoconstricted (had a lower tail skin temperature). In agreement with the enhanced skin vasoconstriction, Trpv1 KO mice had a higher thermoneutral zone. On the behavioral side, Trpv1 KO mice preferred a lower ambient temperature and expressed a higher locomotor activity. Experiments with pharmacological TRPV1 agonists (resiniferatoxin and anandamide) and a TRPV1 antagonist (AMG0347) confirmed that TRPV1 channels located outside the brain tonically inhibit locomotor activity. With age (observed for up to 14 months), the body mass of Trpv1 KO mice exceeded that of controls, sometimes approaching 60 g. In summary, Trpv1 KO mice possess a distinct thermoregulatory phenotype, which is coupled with a predisposition to age-associated overweight and includes hypometabolism, enhanced skin vasoconstriction, decreased thermopreferendum, and hyperkinesis. The latter may be one of the primary deficiencies in Trpv1 KO mice. We propose that TRPV1-mediated signals from the periphery tonically suppress the general locomotor activity.