bims-ciryme 2020-09-13 papers

Nat Commun. 2020 09 07. 11(1): 4448

Cocaine-mediated circadian reprogramming in the striatum through dopamine D2R and PPARγ activation.

Karen Brami-Cherrier, Robert G Lewis, Marlene Cervantes, Yu Liu, Paola Tognini, Pierre Baldi, Paolo Sassone-Corsi, Emiliana Borrelli.

Substance abuse disorders are linked to alteration of circadian rhythms, although the molecular and neuronal pathways implicated have not been fully elucidated. Addictive drugs, such as cocaine, induce a rapid increase of dopamine levels in the brain. Here, we show that acute administration of cocaine triggers reprogramming in circadian gene expression in the striatum, an area involved in psychomotor and rewarding effects of drugs. This process involves the activation of peroxisome protein activator receptor gamma (PPARγ), a nuclear receptor involved in inflammatory responses. PPARγ reprogramming is altered in mice with cell-specific ablation of the dopamine D2 receptor (D2R) in the striatal medium spiny neurons (MSNs) (iMSN-D2RKO). Administration of a specific PPARγ agonist in iMSN-D2RKO mice elicits substantial rescue of cocaine-dependent control of circadian genes. These findings have potential implications for development of strategies to treat substance abuse disorders.

DOI: https://doi.org/10.1038/s41467-020-18200-6

Neuron. 2020 Aug 26. pii: S0896-6273(20)30608-5. [Epub ahead of print]

Circadian VIPergic Neurons of the Suprachiasmatic Nuclei Sculpt the Sleep-Wake Cycle.

Ben Collins, Sara Pierre-Ferrer, Christine Muheim, David Lukacsovich, Yuchen Cai, Andrea Spinnler, Carolina Gutierrez Herrera, Shao'Ang Wen, Jochen Winterer, Mino D C Belle, Hugh D Piggins, Michael Hastings, Andrew Loudon, Jun Yan, Csaba Földy, Antoine Adamantidis, Steven A Brown.

Although the mammalian rest-activity cycle is controlled by a "master clock" in the suprachiasmatic nucleus (SCN) of the hypothalamus, it is unclear how firing of individual SCN neurons gates individual features of daily activity. Here, we demonstrate that a specific transcriptomically identified population of mouse VIP+ SCN neurons is active at the "wrong" time of day-nighttime-when most SCN neurons are silent. Using chemogenetic and optogenetic strategies, we show that these neurons and their cellular clocks are necessary and sufficient to gate and time nighttime sleep but have no effect upon daytime sleep. We propose that mouse nighttime sleep, analogous to the human siesta, is a "hard-wired" property gated by specific neurons of the master clock to favor subsequent alertness prior to dawn (a circadian "wake maintenance zone"). Thus, the SCN is not simply a 24-h metronome: specific populations sculpt critical features of the sleep-wake cycle.

Keywords: alertness; circadian; napping; optogenetics; siesta; sleep; vasoactive intestinal polypeptide; wake maintenance

DOI: https://doi.org/10.1016/j.neuron.2020.08.001

Nat Rev Cancer. 2020 Sep 07.

Metabolic rivalry: circadian homeostasis and tumorigenesis.

Kenichiro Kinouchi, Paolo Sassone-Corsi.

Circadian rhythms govern a large array of physiological and metabolic functions. Perturbations of the daily cycle have been linked to elevated risk of developing cancer as well as poor prognosis in patients with cancer. Also, expression of core clock genes or proteins is remarkably attenuated particularly in tumours of a higher stage or that are more aggressive, possibly linking the circadian clock to cellular differentiation. Emerging evidence indicates that metabolic control by the circadian clock underpins specific hallmarks of cancer metabolism. Indeed, to support cell proliferation and biomass production, the clock may direct metabolic processes of cancer cells in concert with non-clock transcription factors to control how nutrients and metabolites are utilized in a time-specific manner. We hypothesize that the metabolic switch between differentiation or stemness of cancer may be coupled to the molecular clockwork. Moreover, circadian rhythms of host organisms appear to dictate tumour growth and proliferation. This Review outlines recent discoveries of the interplay between circadian rhythms, proliferative metabolism and cancer, highlighting potential opportunities in the development of future therapeutic strategies.

DOI: https://doi.org/10.1038/s41568-020-0291-9