Feillet Céline A, Mendoza Jorge, Pévet Paul, Challet Etienne
Department of Neurobiology of Rhythms, Institute of Cellular and Integrative Neurosciences, Centre National de la Recherche Scientifique, University Louis Pasteur, Strasbourg, France.
Eur J Neurosci. 2008 Dec;28(12):2451-8. doi: 10.1111/j.1460-9568.2008.06538.x.
In mammals, the rhythmic synthesis of melatonin by the pineal gland is tightly controlled by the master clock located in the suprachiasmatic nuclei (SCN). In behaviourally arrhythmic SCN-lesioned rats, we investigated the effects of daily restricted feeding (RF) on pineal melatonin synthesis. RF restored not only a rhythmic transcription of the rate-limiting enzyme for melatonin biosynthesis [arylalkylamine-N-acetyltransferase (AANAT)] and a rhythmic expression of c-FOS but also a rhythmic synthesis of melatonin in the pineal gland. In control rats without functional SCN and fed ad libitum, a daily immobilization stress did not restore any rhythmicity in the pineal gland. Interestingly, a combination of RF and daily stress prior to the time of food access did not markedly impair AaNat mRNA and c-FOS rhythmicity but did abolish the restoration of rhythmic pineal melatonin. These data indicate that the synchronizing effects of RF on the pineal rhythmicity are not due to, and cannot be mimicked by, high levels of circulating glucocorticoids. In keeping with the multi-oscillatory nature of the circadian system, the rhythmicity of pineal melatonin in mammals, until now an exclusive output of the SCN, can also be controlled by daily feeding cues when the SCN clock is lacking. Thus, the present study demonstrates that daily RF in SCN-lesioned rats provides, probably via sympathetic fibres, synchronizing stimuli strong enough to drive rhythmicity in the pineal gland.
在哺乳动物中,松果体褪黑素的节律性合成受位于视交叉上核(SCN)的主时钟严格控制。在行为节律紊乱的SCN损伤大鼠中,我们研究了每日限时进食(RF)对松果体褪黑素合成的影响。RF不仅恢复了褪黑素生物合成限速酶[芳基烷基胺-N-乙酰基转移酶(AANAT)]的节律性转录和c-FOS的节律性表达,还恢复了松果体中褪黑素的节律性合成。在无功能SCN且自由进食的对照大鼠中,每日固定应激并未恢复松果体的任何节律性。有趣的是,在进食时间之前将RF与每日应激相结合,并未显著损害AaNat mRNA和c-FOS的节律性,但确实消除了松果体褪黑素节律性的恢复。这些数据表明,RF对松果体节律性的同步作用并非由于循环糖皮质激素水平升高所致,也不能被其模拟。与昼夜节律系统的多振荡性质一致,哺乳动物松果体褪黑素的节律性,此前一直是SCN的唯一输出,当SCN时钟缺失时,也可由每日进食信号控制。因此,本研究表明,SCN损伤大鼠的每日RF可能通过交感神经纤维提供足够强的同步刺激,以驱动松果体的节律性。