Yoshida Ayaka, Furube Eriko, Mannari Tetsuya, Takayama Yasunori, Kittaka Hiroki, Tominaga Makoto, Miyata Seiji
Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan.
Division of Cell Signaling, Okazaki Institute for Integrative Bioscience, (National Institute for Physiological Sciences), National Institute of Natural Sciences, Okazaki, Aichi 444-8787, Japan.
Sci Rep. 2016 May 18;6:26088. doi: 10.1038/srep26088.
Transient receptor potential vanilloid receptor 1 (TRPV1) is a non-selective cation channel that is stimulated by heat (>43 °C), mechanical/osmotic stimuli, and low pH. The importance of TRPV1 in inflammatory responses has been demonstrated, whereas its participation in brains remains unclear. In the present study, the intracerebroventricular (icv) administration of the TRPV1 agonist resiniferatoxin (RTX) induced the activation of signal transducer and activator of transcription 3 (STAT3) in circumventricular organs (CVOs) and thermoregulation-associated brain regions with a similar patttern to the peripheral and icv administration of lipopolysaccharide (LPS). With the peripheral and icv LPS stimuli, STAT3 activation was significantly lower in Trpv1(-/-) mice than in Trpv1(+/+) mice. The icv administration of RTX induced transient hypothermia, whereas that of the TRPV1 antagonist capsazepine enhanced the magnitude and period of LPS-induced hyperthermia. These results indicate that TRPV1 is important for activating proinflammatory STAT3 signaling and thermoregulation-associated brain pathways in the brain.
瞬时受体电位香草酸受体1（TRPV1）是一种非选择性阳离子通道，可被热（>43°C）、机械/渗透刺激和低pH值激活。TRPV1在炎症反应中的重要性已得到证实，但其在大脑中的作用仍不清楚。在本研究中，经脑室（icv）注射TRPV1激动剂树脂毒素（RTX）可诱导室周器官（CVO）和体温调节相关脑区中信号转导和转录激活因子3（STAT3）的激活，其模式与外周和icv注射脂多糖（LPS）相似。在外周和icv给予LPS刺激时，Trpv1（-/-）小鼠的STAT3激活明显低于Trpv1（+/+）小鼠。icv注射RTX可诱导短暂性体温过低，而TRPV1拮抗剂辣椒素则增强了LPS诱导的体温过高的幅度和持续时间。这些结果表明，TRPV1对于激活大脑中的促炎STAT3信号和体温调节相关脑通路很重要。
