Yannielli Paola C, Molyneux Penny C, Harrington Mary E, Golombek Diego A
Universidad Nacional de Quilmes/Consejo Nacional de Investigaciones Científicas y Técnicas, Bernal, 1876 Buenos Aires, Argentina.
J Neurosci. 2007 Mar 14;27(11):2890-5. doi: 10.1523/JNEUROSCI.3913-06.2007.
The orexigenic peptide ghrelin stimulates both food intake and growth hormone release and is synthesized in the stomach and in hypothalamic areas involved in feeding control. The suprachiasmatic nuclei of the hypothalamus (SCN) control most circadian rhythms, although there is evidence that some oscillators, such as food-entrainable oscillators, can drive activity rhythms even after SCN ablation. Ghrelin levels exhibit a circadian rhythm and closely follow feeding schedules, making this peptide a putative candidate for food-related entraining signals. We examined the response of the SCN to ghrelin treatments in vitro, by means of electrophysiological and bioluminescence recordings, and in vivo, by assessing effects on the phase of locomotor activity rhythms. Ghrelin applied at circadian time 6 in vitro to cultured SCN slices induced an approximately 3 h phase advance. In addition, ghrelin phase advanced the rhythm of PER2::LUC (Period2::Luciferase) expression in cultured SCN explants from mPer2(Luc) transgenic mice. In vivo, intraperitoneal administration of ghrelin or a synthetic analog, growth hormone-releasing protein-6 (GHRP-6), to ad libitum fed animals failed to alter circadian phase. When injected after 30 h of food deprivation, GHRP-6 induced a phase advance compared with saline-injected animals. These results indicate that ghrelin may play a role in the circadian system by exerting a direct action on the SCN and that the system as a whole may become sensitive to ghrelin and other feeding-related neuropeptides under conditions of food restriction.
食欲肽胃饥饿素可刺激食物摄入和生长激素释放，它在胃以及参与进食控制的下丘脑区域合成。下丘脑的视交叉上核（SCN）控制着大多数昼夜节律，不过有证据表明，一些振荡器，如食物可调节的振荡器，即使在SCN被切除后仍能驱动活动节律。胃饥饿素水平呈现昼夜节律，并紧密跟随进食时间表，这使得这种肽成为与食物相关的同步信号的一个假定候选者。我们通过电生理和生物发光记录在体外研究了SCN对胃饥饿素处理的反应，并通过评估对运动活动节律相位的影响在体内进行了研究。在体外，于昼夜时间6将胃饥饿素应用于培养的SCN切片，可诱导约3小时的相位提前。此外，胃饥饿素使来自mPer2（Luc）转基因小鼠的培养SCN外植体中PER2::LUC（周期蛋白2::荧光素酶）表达的节律发生相位提前。在体内，对自由进食的动物腹腔注射胃饥饿素或一种合成类似物生长激素释放蛋白-6（GHRP-6）未能改变昼夜节律相位。当在禁食30小时后注射时，与注射生理盐水的动物相比，GHRP-6诱导了相位提前。这些结果表明，胃饥饿素可能通过对SCN施加直接作用而在昼夜节律系统中发挥作用，并且在食物限制条件下，整个系统可能会对胃饥饿素和其他与进食相关的神经肽变得敏感。
