Instituto de Investigaciones Biomedicas, UNAM, Ciudad Universitaria , 04510 Mexico DF , Mexico.
Departamento de Anatomia, Facultad de Medicina, UNAM, Ciudad Universitaria , 04510 Mexico DF , Mexico.
eNeuro. 2017 Mar 24;4(2). doi: 10.1523/ENEURO.0028-17.2017. eCollection 2017 Mar-Apr.
The suprachiasmatic nucleus (SCN) is generally considered the master clock, independently driving all circadian rhythms. We recently demonstrated the SCN receives metabolic and cardiovascular feedback adeptly altering its neuronal activity. In the present study, we show that microcuts effectively removing SCN-arcuate nucleus (ARC) interconnectivity in Wistar rats result in a loss of rhythmicity in locomotor activity, corticosterone levels, and body temperature in constant dark (DD) conditions. Elimination of these reciprocal connections did not affect SCN clock gene rhythmicity but did cause the ARC to desynchronize. Moreover, unilateral SCN lesions with contralateral retrochiasmatic microcuts resulted in identical arrhythmicity, proving that for the expression of physiological rhythms this reciprocal SCN-ARC interaction is essential. The unaltered SCN c-Fos expression following glucose administration in disconnected animals as compared to a significant decrease in controls demonstrates the importance of the ARC as metabolic modulator of SCN neuronal activity. Together, these results indicate that the SCN is more than an autonomous clock, and forms an essential component of a larger network controlling homeostasis. The present novel findings illustrate how an imbalance between SCN and ARC communication through circadian disruption could be involved in the etiology of metabolic disorders.
视交叉上核(SCN)通常被认为是主时钟,独立驱动所有的昼夜节律。我们最近证明,SCN 能够敏锐地接收代谢和心血管反馈,从而改变其神经元活动。在本研究中,我们表明,在 Wistar 大鼠中,有效的微切割可以有效地去除 SCN-弓状核(ARC)的相互连接,导致在持续黑暗(DD)条件下的运动活动、皮质酮水平和体温失去节律性。消除这些相互连接不会影响 SCN 时钟基因的节律性,但会导致 ARC 去同步。此外,单侧 SCN 损伤伴对侧视交叉后微切割导致相同的心律失常,证明对于生理节律的表达,这种 SCN-ARC 相互作用是必不可少的。与对照组相比,在断开的动物中,葡萄糖给药后 SCN 的 c-Fos 表达不变,这表明 ARC 作为 SCN 神经元活动的代谢调节剂的重要性。总之,这些结果表明,SCN 不仅仅是一个自主的时钟,而是一个控制体内平衡的更大网络的重要组成部分。目前的新发现表明,通过昼夜节律中断,SCN 和 ARC 之间的通信失衡如何参与代谢紊乱的病因。