bims-ciryme 2019-03-17 papers

Biology (Basel). 2019 Mar 11. pii: E13. [Epub ahead of print]8(1):

The Mammalian Circadian Timing System and the Suprachiasmatic Nucleus as Its Pacemaker.

Michael H Hastings, Elizabeth S Maywood, Marco Brancaccio.

The past twenty years have witnessed the most remarkable breakthroughs in our understanding of the molecular and cellular mechanisms that underpin circadian (approximately one day) time-keeping. Across model organisms in diverse taxa: cyanobacteria (Synechococcus), fungi (Neurospora), higher plants (Arabidopsis), insects (Drosophila) and mammals (mouse and humans), a common mechanistic motif of delayed negative feedback has emerged as the Deus ex machina for the cellular definition of ca. 24 h cycles. This review will consider, briefly, comparative circadian clock biology and will then focus on the mammalian circadian system, considering its molecular genetic basis, the properties of the suprachiasmatic nucleus (SCN) as the principal circadian clock in mammals and its role in synchronising a distributed peripheral circadian clock network. Finally, it will consider new directions in analysing the cell-autonomous and circuit-level SCN clockwork and will highlight the surprising discovery of a central role for SCN astrocytes as well as SCN neurons in controlling circadian behaviour.

Keywords: Bmal1; astrocytes; clock; cryptochrome; entrainment; period; photoperiod; sleep; suprachiasmatic

DOI: https://doi.org/10.3390/biology8010013

Front Neurosci. 2019 ;13 139

The Network Mechanism of the Central Circadian Pacemaker of the SCN: Do AVP Neurons Play a More Critical Role Than Expected?

Michihiro Mieda.

The suprachiasmatic nucleus (SCN) functions as the central circadian pacemaker in mammals and entrains to the environmental light/dark cycle. It is composed of multiple types of GABAergic neurons, and interneuronal communications among these neurons are essential for the circadian pacemaking of the SCN. However, the mechanisms underlying the SCN neuronal network remain unknown. This review will provide a brief overview of the current knowledge concerning the differential roles of multiple neuropeptides and neuropeptide-expressing neurons in the SCN, especially focusing on the emerging roles of arginine vasopressin-producing neurons uncovered by recent studies utilizing neuron type-specific genetic manipulations in mice.

Keywords: circadian rhythm; neural network; suprachiasmatic nucleus; vasoactive intestinal peptide; vasopressin

DOI: https://doi.org/10.3389/fnins.2019.00139

Sci Rep. 2019 Mar 14. 9(1): 4428

Circadian and wake-dependent changes in human plasma polar metabolites during prolonged wakefulness: A preliminary analysis.

Leilah K Grant, Suzanne Ftouni, Brunda Nijagal, David P De Souza, Dedreia Tull, Malcolm J McConville, Shantha M W Rajaratnam, Steven W Lockley, Clare Anderson.

Establishing circadian and wake-dependent changes in the human metabolome are critical for understanding and treating human diseases due to circadian misalignment or extended wake. Here, we assessed endogenous circadian rhythms and wake-dependent changes in plasma metabolites in 13 participants (4 females) studied during 40-hours of wakefulness. Four-hourly plasma samples were analyzed by hydrophilic interaction liquid chromatography (HILIC)-LC-MS for 1,740 metabolite signals. Group-averaged (relative to DLMO) and individual participant metabolite profiles were fitted with a combined cosinor and linear regression model. In group-level analyses, 22% of metabolites were rhythmic and 8% were linear, whereas in individual-level analyses, 14% of profiles were rhythmic and 4% were linear. We observed metabolites that were significant at the group-level but not significant in a single individual, and metabolites that were significant in approximately half of individuals but not group-significant. Of the group-rhythmic and group-linear metabolites, only 7% and 12% were also significantly rhythmic or linear, respectively, in ≥50% of participants. Owing to large inter-individual variation in rhythm timing and the magnitude and direction of linear change, acrophase and slope estimates also differed between group- and individual-level analyses. These preliminary findings have important implications for biomarker development and understanding of sleep and circadian regulation of metabolism.

DOI: https://doi.org/10.1038/s41598-019-40353-8