bims-ciryme 2021-04-11 papers

Nat Commun. 2021 Apr 09. 12(1): 2113

Adenosine integrates light and sleep signalling for the regulation of circadian timing in mice.

The accumulation of adenosine is strongly correlated with the need for sleep and the detection of sleep pressure is antagonised by caffeine. Caffeine also affects the circadian timing system directly and independently of sleep physiology, but how caffeine mediates these effects upon the circadian clock is unclear. Here we identify an adenosine-based regulatory mechanism that allows sleep and circadian processes to interact for the optimisation of sleep/wake timing in mice. Adenosine encodes sleep history and this signal modulates circadian entrainment by light. Pharmacological and genetic approaches demonstrate that adenosine acts upon the circadian clockwork via adenosine A1/A2A receptor signalling through the activation of the Ca2+ -ERK-AP-1 and CREB/CRTC1-CRE pathways to regulate the clock genes Per1 and Per2. We show that these signalling pathways converge upon and inhibit the same pathways activated by light. Thus, circadian entrainment by light is systematically modulated on a daily basis by sleep history. These findings contribute to our understanding of how adenosine integrates signalling from both light and sleep to regulate circadian timing in mice.

DOI: https://doi.org/10.1038/s41467-021-22179-z

Front Endocrinol (Lausanne). 2021 ;12 662017

Astrocyte Clocks and Glucose Homeostasis.

Olga Barca-Mayo, Miguel López.

The endogenous timekeeping system evolved to anticipate the time of the day through the 24 hours cycle of the Earth's rotation. In mammals, the circadian clock governs rhythmic physiological and behavioral processes, including the daily oscillation in glucose metabolism, food intake, energy expenditure, and whole-body insulin sensitivity. The results from a series of studies have demonstrated that environmental or genetic alterations of the circadian cycle in humans and rodents are strongly associated with metabolic diseases such as obesity and type 2 diabetes. Emerging evidence suggests that astrocyte clocks have a crucial role in regulating molecular, physiological, and behavioral circadian rhythms such as glucose metabolism and insulin sensitivity. Given the concurrent high prevalence of type 2 diabetes and circadian disruption, understanding the mechanisms underlying glucose homeostasis regulation by the circadian clock and its dysregulation may improve glycemic control. In this review, we summarize the current knowledge on the tight interconnection between the timekeeping system, glucose homeostasis, and insulin sensitivity. We focus specifically on the involvement of astrocyte clocks, at the organism, cellular, and molecular levels, in the regulation of glucose metabolism.

Keywords: astrocytes; circadian clock; diabetes; glucose homeostasis; metabolism

DOI: https://doi.org/10.3389/fendo.2021.662017

Front Neurosci. 2021 ;15 659974

Genesis of the Master Circadian Pacemaker in Mice.

Arthur H Cheng, Hai-Ying Mary Cheng.

The suprachiasmatic nucleus (SCN) of the hypothalamus is the central circadian clock of mammals. It is responsible for communicating temporal information to peripheral oscillators via humoral and endocrine signaling, ultimately controlling overt rhythms such as sleep-wake cycles, body temperature, and locomotor activity. Given the heterogeneity and complexity of the SCN, its genesis is tightly regulated by countless intrinsic and extrinsic factors. Here, we provide a brief overview of the development of the SCN, with special emphasis on the murine system.

Keywords: development; neurogenesis; neuronal differentiation; neuropeptides; suprachiasmatic nucleus; transcription factors

DOI: https://doi.org/10.3389/fnins.2021.659974

Front Physiol. 2021 ;12 641461

Sex Differences in Rest-Activity Circadian Rhythm in Patients With Metabolic Syndrome.

Antonino Mulè, Eleonora Bruno, Patrizia Pasanisi, Letizia Galasso, Lucia Castelli, Andrea Caumo, Fabio Esposito, Eliana Roveda, Angela Montaruli.

Rest-Activity circadian Rhythm (RAR) can be used as a marker of the circadian timing system. Recent studies investigated the relationship between irregular circadian rhythms and cardiovascular risk factors such as hypertension, obesity, and dyslipidemia. These factors are related to the Metabolic Syndrome (MS), a clustering of metabolic risk factors that increases the risk of several cardiovascular and metabolic diseases. This cross-sectional analysis aimed to explore the RAR characteristics by actigraphy in subjects with MS, particularly in relation to sex and MS parameters, using parametric and non-parametric analyses. Distinguishing the characteristics of RAR based on sex could prove useful as a tool to improve the daily level of activity and set up customized activity programs based on each person's circadian activity profile. This study showed that female participants exhibited higher values than male participants in the Midline Estimating Statistic of Rhythm (MESOR) (243.3 ± 20.0 vs 197.6 ± 17.9 activity count), Amplitude (184.5 ± 18.5 vs 144.2 ± 17.2 activity count), which measures half of the extent of the rhythmic variation in a cycle, and the most active 10-h period (M10) (379.08 ± 16.43 vs 295.13 ± 12.88 activity count). All these parameters are indicative of a higher daily activity level in women. Female participants also had lower Intradaily Variability (IV) than male participants (0.75 ± 0.03 vs 0.85 ± 0.03 activity count), which indicates a more stable and less fragmented RAR. These preliminary data provide the first experimental evidence of a difference in RAR parameters between male and female people with MS.

Keywords: actigraphy; activity level; chronobiology; circadian rhythms; gender differences; intradaily variability; metabolic syndrome; rest-activity circadian rhythm

DOI: https://doi.org/10.3389/fphys.2021.641461