bims-ciryme 2020-04-26 papers

Issue of 2020‒04‒26
two papers selected by
Gabriela Da Silva Xavier
University of Birmingham

J Mol Biol. 2020 Apr 15. pii: S0022-2836(20)30280-1. [Epub ahead of print]

Molecular Links between the Circadian Clock and the Cell Cycle.

Elham Farshadi, Gijsbertus T J van der Horst, Inês Chaves.

Circadian control of cell division is well established in diverse organisms. Recent single cell studies on mouse fibroblasts have shown that the circadian clock and cell cycle systems are robustly phase-coupled in a bidirectional manner. In healthy cells, coupling of clock and cell cycle results in timed mitosis and rhythmic DNA replication. However, little is known about the interplay between these two oscillators in cancer cells, which often display de-regulated cell proliferation and circadian gene expression. Here we review the molecular organization of the circadian clock and the cell cycle, as well as the reciprocal interaction between the circadian clock and the cell cycle in normal and in cancer cells. Understanding how the circadian clock and cell cycle are coupled in cancer cells will be instrumental to optimally take advantage of chronotherapy in cancer treatment, as efficiency of therapy benefits from asynchrony in timed mitosis between the host and the malignant cells in order to predict the optimal time of treatment.

Keywords: Cancer; Cell cycle; Chronotherapy; Circadian clock; Coupling

DOI: https://doi.org/10.1016/j.jmb.2020.04.003

Elife. 2020 Apr 21. pii: e54275. [Epub ahead of print]9

Dual orexin and MCH neuron-ablated mice display severe sleep attacks and cataplexy.

Chi Jung Hung, Daisuke Ono, Thomas S Kilduff, Akihiro Yamanaka.

Orexin/hypocretin-producing and melanin-concentrating hormone-producing (MCH) neurons are co-extensive in the hypothalamus and project throughout the brain to regulate sleep/wakefulness. Ablation of orexin neurons decreases wakefulness and results in a narcolepsy-like phenotype, whereas ablation of MCH neurons increases wakefulness. Since it is unclear how orexin and MCH neurons interact to regulate sleep/wakefulness, we generated transgenic mice in which both orexin and MCH neurons could be ablated. Double-ablated mice exhibited increased wakefulness and decreased both rapid eye movement (REM) and non-REM (NREM) sleep. Double-ablated mice showed severe cataplexy compared with orexin neuron-ablated mice, suggesting that MCH neurons normally suppress cataplexy. Double-ablated mice also showed frequent sleep attacks with elevated spectral power in the delta and theta range, a unique state that we call 'delta-theta sleep'. Together, these results indicate a functional interaction between orexin and MCH neurons in vivo that suggests the synergistic involvement of these neuronal populations in the sleep/wakefulness cycle.

Keywords: ablation; mch neurons; mouse; narcolepsy; neuroscience; orexin/hypocretin neurons; sleep; transgenic animals

DOI: https://doi.org/10.7554/eLife.54275