Mutoh Tatsushi, Shibata Shigenobu, Korf Horst-Werner, Okamura Hitoshi
Division of Molecular Brain Science, Department of Brain Sciences, Kobe University Graduate School of Medicine, Chuo-ku, Kobe 650-0017, Japan.
J Physiol. 2003 Feb 15;547(Pt 1):317-32. doi: 10.1113/jphysiol.2002.028001. Epub 2003 Jan 10.
In mammals, the autonomic nervous system mediates the central circadian clock oscillation from the suprachiasmatic nucleus (SCN) to the peripheral organs, and controls cardiovascular, respiratory and gastrointestinal functions. The present study was conducted in mice to address whether light signals conveyed to the SCN can control peripheral autonomic functions, and further examined the impact of centrally administered melatonin on peripheral autonomic functions via activation of melatonin receptor signalling. In vivo electrophysiological techniques were performed in anaesthetised, open-chest and artificially ventilated mice whilst monitoring the arterial blood pressure and heart rate. Light induced an increase of the renal sympathetic nerve activity, arterial blood pressure and heart rate immediately after lights on. Conversely, light rapidly suppressed the gastric vagal parasympathetic nerve activity, which was affected neither by hepatic vagotomy nor by total subdiaphragmatic vagotomy. These autonomic responses were mediated by the SCN since bilateral SCN lesion totally abolished the light-evoked neuronal and cardiovascular responses. Melatonin administered intracerebroventricularly (I.C.V.) attenuated the sympathetic and vagal nerve activities in a dose-dependent manner with a threshold of 0.1 ng and these effects were blocked by I.C.V. pre-treatment of the competitive melatonin receptor antagonist luzindole. These results suggest that light induces sympathoexcitation and vagal suppression through the SCN and that melatonin modulates the light-induced autonomic responses via activation of the central melatonin receptor signalling.
在哺乳动物中,自主神经系统介导从视交叉上核(SCN)到外周器官的中枢昼夜节律振荡,并控制心血管、呼吸和胃肠功能。本研究在小鼠中进行,以探讨传递至SCN的光信号是否能控制外周自主功能,并进一步研究通过激活褪黑素受体信号通路中枢给予褪黑素对外周自主功能的影响。在麻醉、开胸并人工通气的小鼠中采用体内电生理技术,同时监测动脉血压和心率。光照开启后,光立即引起肾交感神经活动、动脉血压和心率增加。相反,光迅速抑制胃迷走副交感神经活动,该活动不受肝迷走神经切断术或完全膈下迷走神经切断术的影响。这些自主反应由SCN介导,因为双侧SCN损伤完全消除了光诱发的神经元和心血管反应。脑室内(I.C.V.)给予褪黑素以剂量依赖性方式减弱交感神经和迷走神经活动,阈值为0.1 ng,且这些作用被I.C.V.预先给予的竞争性褪黑素受体拮抗剂鲁辛朵尔阻断。这些结果表明,光通过SCN诱导交感兴奋和迷走抑制,且褪黑素通过激活中枢褪黑素受体信号通路调节光诱导的自主反应。