bims-ciryme 2019-03-24 papers

Cell Rep. 2019 Mar 19. pii: S2211-1247(19)30247-5. [Epub ahead of print]26(12): 3191-3202.e8

SOX2-Dependent Transcription in Clock Neurons Promotes the Robustness of the Central Circadian Pacemaker.

Arthur H Cheng, Pascale Bouchard-Cannon, Sara Hegazi, Christopher Lowden, Samuel W Fung, Cheng-Kang Chiang, Rob W Ness, Hai-Ying Mary Cheng.

Clock neurons within the mammalian suprachiasmatic nuclei (SCN) encode circadian time using interlocked transcription-translation feedback loops (TTFLs) that drive rhythmic gene expression. However, the contributions of other transcription factors outside of the circadian TTFLs to the functionality of the SCN remain obscure. Here, we report that the stem and progenitor cell transcription factor, sex-determining region Y-box 2 (SOX2), is expressed in adult SCN neurons and positively regulates transcription of the core clock gene, Period2. Mice lacking SOX2 selectively in SCN neurons display imprecise, poorly consolidated behavioral rhythms that do not entrain efficiently to environmental light cycles and that are highly susceptible to constant light-induced arrhythmicity. RNA sequencing revealed that Sox2 deficiency alters the SCN transcriptome, reducing the expression of core clock genes and neuropeptide-receptor systems. By defining the transcriptional landscape within SCN neurons, SOX2 enables the generation of robust, entrainable circadian rhythms that accurately reflect environmental time.

Keywords: PERIOD2; RNA sequencing; SOX2; behavior; circadian rhythms; stem cell transcription factor; suprachiasmatic nucleus; transcription

DOI: https://doi.org/10.1016/j.celrep.2019.02.068

Auton Neurosci. 2019 May;pii: S1566-0702(18)30283-2. [Epub ahead of print]218 43-50

The suprachiasmatic nucleus; a responsive clock regulating homeostasis by daily changing the setpoints of physiological parameters.

Ruud M Buijs, Mara A Guzmán Ruiz, Rebeca Méndez Hernández, Betty Rodríguez Cortés.

The suprachiasmatic nucleus (SCN) is responsible for determining circadian variations in physiological setpoints. The SCN achieves such control through projections to different target structures within and outside the hypothalamus. Thus the SCN prepares the physiology of the body every 24 h via hormones and autonomic nervous system (ANS), to coming changes in behavior. Resulting rhythms in hormones and ANS activity transmit a precise message to selective organs, adapting their sensitivity to coming hormones, metabolites or other essentials. Thus the SCN as autonomous clock gives rhythm to physiological processes. However when the body is challenged by infections, low or high temperature, food shortage or excess: physiological setpoints need to be changed. For example, under fasting conditions, setpoints for body temperature and glucose levels are lowered at the beginning of the sleep (inactive) phase. However, starting the active phase, a normal increase in glucose and temperature levels take place to support activities associated with the acquisition of food. Thus, the SCN adjusts physiological setpoints in agreement with time of the day and according to challenges faced by the body. The SCN is enabled to do this by receiving extensive input from brain areas involved in sensing the condition of the body. Therefore, when the body receives stimuli contradicting normal physiology, such as eating or activity during the inactive period, this information reaches the SCN, adapting its output to correct this disbalance. As consequence frequent violations of the SCN message, such as by shift work or night eating, will result in development of disease.

Keywords: Autonomic nervous system; Blood pressure; Circadian rhythm; Circumventricular organs; Corticosterone; Sympathetic; Temperature; Vagus

DOI: https://doi.org/10.1016/j.autneu.2019.02.001

Biology (Basel). 2019 Mar 21. pii: E18. [Epub ahead of print]8(1):

Telling the Time with a Broken Clock: Quantifying Circadian Disruption in Animal Models.

Laurence A Brown, Angus S Fisk, Carina A Pothecary, Stuart N Peirson.

Circadian rhythms are approximately 24 h cycles in physiology and behaviour that enable organisms to anticipate predictable rhythmic changes in their environment. These rhythms are a hallmark of normal healthy physiology, and disruption of circadian rhythms has implications for cognitive, metabolic, cardiovascular and immune function. Circadian disruption is of increasing concern, and may occur as a result of the pressures of our modern 24/7 society-including artificial light exposure, shift-work and jet-lag. In addition, circadian disruption is a common comorbidity in many different conditions, ranging from aging to neurological disorders. A key feature of circadian disruption is the breakdown of robust, reproducible rhythms with increasing fragmentation between activity and rest. Circadian researchers have developed a range of methods for estimating the period of time series, typically based upon periodogram analysis. However, the methods used to quantify circadian disruption across the literature are not consistent. Here we describe a range of different measures that have been used to measure circadian disruption, with a particular focus on laboratory rodent data. These methods include periodogram power, variability in activity onset, light phase activity, activity bouts, interdaily stability, intradaily variability and relative amplitude. The strengths and limitations of these methods are described, as well as their normal ranges and interrelationships. Whilst there is an increasing appreciation of circadian disruption as both a risk to health and a potential therapeutic target, greater consistency in the quantification of disrupted rhythms is needed.

Keywords: activity bouts; data analysis; entrainment; fragmentation; periodogram

DOI: https://doi.org/10.3390/biology8010018