Hypothalamic warm-sensitive neurons require TRPC4 channel for detecting internal warmth and regulating body temperature in mice
Hypothalamic warm-sensitive neurons require TRPC4 channel for detecting internal warmth and regulating body temperature in mice
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DOI：
10.1016/j.neuron.2022.11.008
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发表时间：
2023-02-01
期刊：
影响因子：
16.2
通讯作者：
Shen, Wei L.
中科院分区：
文献类型：
--
作者：
Zhou, Qian;Fu, Xin;Shen, Wei L.
精确监测内部温度对于哺乳动物的热稳态至关重要。几十年来，视前区（POA）内的温敏神经元（WSNs）被认为可以感知内部的温暖，并将此信息作为反馈来调节体温（Tcore）。然而，无线传感器网络测量温度的细胞和分子机制在很大程度上仍然不确定。通过一个试点的遗传筛选，我们发现，沉默TRPC 4通道在小鼠中大大减弱低温诱导的光介导的加热的POA。TRPC 4的功能丧失研究证实了其在GABA能WSN中的温感作用，导致基础温度设置，温防御和发热反应的额外缺陷。此外，TRPC 4拮抗剂和激动剂双向调节Tcore。因此，我们的数据表明，TRPC4是必不可少的内部温暖和TRPC4表达GABA能无线传感器作为一种新的细胞传感器的功能，防止Tcore超过设定点温度。TRPC 4可能代表用于管理Tcore的潜在治疗靶点。
Precise monitoring of internal temperature is vital for thermal homeostasis in mammals. For decades, warm -sensitive neurons (WSNs) within the preoptic area (POA) were thought to sense internal warmth, using this information as feedback to regulate body temperature (Tcore). However, the cellular and molecular mecha-nisms by which WSNs measure temperature remain largely undefined. Via a pilot genetic screen, we found that silencing the TRPC4 channel in mice substantially attenuated hypothermia induced by light-mediated heating of the POA. Loss-of-function studies of TRPC4 confirmed its role in warm sensing in GABAergic WSNs, causing additional defects in basal temperature setting, warm defense, and fever responses. Further-more, TRPC4 antagonists and agonists bidirectionally regulated Tcore. Thus, our data indicate that TRPC4 is essential for sensing internal warmth and that TRPC4-expressing GABAergic WSNs function as a novel cellular sensor for preventing Tcore from exceeding set-point temperatures. TRPC4 may represent a potential therapeutic target for managing Tcore.