bims-ciryme 2019-04-21 papers

Cell Rep. 2019 Apr 16. pii: S2211-1247(19)30394-8. [Epub ahead of print]27(3): 649-657.e5

Rhythmic Food Intake Drives Rhythmic Gene Expression More Potently than the Hepatic Circadian Clock in Mice.

Ben J Greenwell, Alexandra J Trott, Joshua R Beytebiere, Shanny Pao, Alexander Bosley, Erin Beach, Patrick Finegan, Christopher Hernandez, Jerome S Menet.

Every mammalian tissue exhibits daily rhythms in gene expression to control the activation of tissue-specific processes at the most appropriate time of the day. Much of this rhythmic expression is thought to be driven cell autonomously by molecular circadian clocks present throughout the body. By manipulating the daily rhythm of food intake in the mouse, we here show that more than 70% of the cycling mouse liver transcriptome loses rhythmicity under arrhythmic feeding. Remarkably, core clock genes are not among the 70% of genes losing rhythmic expression, and their expression continues to exhibit normal oscillations in arrhythmically fed mice. Manipulation of rhythmic food intake also alters the timing of key signaling and metabolic pathways without altering the hepatic clock oscillations. Our findings thus demonstrate that systemic signals driven by rhythmic food intake significantly contribute to driving rhythms in liver gene expression and metabolic functions independently of the cell-autonomous hepatic clock.

Keywords: RNA-seq; biological rhythms; circadian clock; feeding behavior; lipogenesis; liver; mTOR; mouse; temporal restricted feeding; transcription

DOI: https://doi.org/10.1016/j.celrep.2019.03.064

Front Physiol. 2019 ;10 361

Modulation of NMDA-Mediated Clock Resetting in the Suprachiasmatic Nuclei of mPer2 Luc Mouse by Endocannabinoids.

Martin Sládek, Alena Sumová.

Light entrains the master circadian clock in the suprachiasmatic nucleus (SCN) predominantly through glutamatergic signaling via NMDA receptors. The magnitude and the direction of resulting phase shifts depend on timing of the photic stimulus. Previous reports based on behavioral and electrophysiological data suggested that endocannabinoids (EC) might reduce the ability of the SCN clock to respond to light. However, there is little direct evidence for the involvement of EC in entrainment of the rhythmic clock gene expression in the SCN. We have used luminescence recording of cultured SCN slices from mPer2 Luc mice to construct a complete phase response curve (PRC) for NMDA receptor activation. The results demonstrated that NMDA administration phase-shifts the PER2 rhythm in a time-specific manner. A stable "singularity," in the course of which the clock seemingly stops while the overall phase is caught between delays and advances, can occur in response to NMDA at a narrow interval during the PER2 level decrease. NMDA-induced phase delays were affected neither by the agonist (WIN 55,212-2 mesylate) nor by the antagonist (rimonabant hydrochloride) of EC receptors. However, the agonist significantly reduced the NMDA-induced phase advance of the clock, while the antagonist enhanced the phase advance, causing a shift in the sensitivity window of the SCN to NMDA. The modulation of EC signaling in the SCN had no effect by itself on the phase of the PER2 rhythm. The results provide evidence for a modulatory role of EC in photic entrainment of the circadian clock in the SCN.

Keywords: NMDA; PER2::LUC; circadian; endocannabinoids; entrainment; glutamate receptor; phase response curve; suprachiasmatic nucleus

DOI: https://doi.org/10.3389/fphys.2019.00361

Front Neuroendocrinol. 2019 Apr 16. pii: S0091-3022(19)30010-X. [Epub ahead of print]

Circadian regulation of depression: a role for serotonin.

Rachel A Daut, Laura K Fonken.

Synchronizing circadian (24 h) rhythms in physiology and behavior with the environmental light-dark cycle is critical for maintaining optimal health. Dysregulation of the circadian system increases susceptibility to numerous pathological conditions including major depressive disorder. Stress is a common etiological factor in the development of depression and the circadian system is highly interconnected to stress-sensitive neurotransmitter systems such as the serotonin (5-hydroxytryptamine, 5-HT) system. Thus, here we propose that stress-induced perturbation of the 5-HT system disrupts circadian processes and increases susceptibility to depression. In this review, we first provide an overview of the basic components of the circadian system. Next, we discuss evidence that circadian dysfunction is associated with changes in mood in humans and rodent models. Finally, we provide evidence that 5-HT is a critical factor linking dysregulation of the circadian system and mood. Determining how these two systems interact may provide novel therapeutic targets for depression.

Keywords: circadian rhythms; depression; mood; resilience; serotonin

DOI: https://doi.org/10.1016/j.yfrne.2019.04.003