Trends in Neurosciences
ReviewTime after time: inputs to and outputs from the mammalian circadian oscillators
Section snippets
The same but different – the basic clockwork in the SCN and peripheral tissues
The components of the mammalian circadian oscillator have been studied primarily using mice carrying mutations in one or more of the clock genes. The components can be assembled into a basic wiring diagram (Fig. 1a) that involves a complex transcriptional feedback circuit of three period genes (per1, per2 and per3), two cryptochrome genes (cry1 and cry2), a clock gene (clk) and the gene encoding brain–muscle Arnt-like protein 1 (bmal1) 1., 4., 6., 7.. Levels of all the transcripts (except those
Seeing the light – identifying the photoreceptor for light input to the clock
The identity of the photopigment involved in light signaling to the mammalian circadian system has long been a mystery [36]. Cryptochromes, which have been firmly implicated as circadian photopigments in Drosophila [37] and zebrafish [38], do not seem to be essential in mammals [39]. Another interesting candidate, melanopsin, was found to be expressed specifically in the ganglion cell layer of the retina 40., 41.. This appeared important as a number of previous studies had localized the site of
Getting the word out – synchronizing oscillations in the periphery
The role of the SCN as a master timer in the circadian system implies that timing cues are continually transmitted to the rest of the body. At least part of this timing information is transmitted to other areas of the brain via physical connections [58]. One recent study has traced an indirect link from the SCN through the dorsomedial hypothalamic nucleus to the noradrenergic nucleus locus coeruleus, which is involved in regulating arousal state [59]. The neurons of the SCN have a higher
They've got rhythm – circadian gene expression in peripheral tissues
Independently of how timing signals arrive, to have any functional relevance the cells within various peripheral tissues must be able to do different things at different times of day. Several peripheral tissues have now been shown to regulate gene expression on a daily basis. Transcript profiling in serum-shocked synchronized fibroblasts 74., 75., heart [76], liver 67., 76., 77., 78., kidney [79] and the SCN itself [67] have all been reported. Several global conclusions can be drawn from this
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Circadian and Circannual Regulation in the Horse: Internal Timing in an Elite Athlete
2019, Journal of Equine Veterinary ScienceCitation Excerpt :This 24-hour oscillation, and those of almost every other tissue cell, is produced by core and accessory transcriptional/translational feedback loops involving a set of core clock genes, with Bmal1 and Clock acting as positive elements and Per1, Cry1, Cry2, and Nr1d1 acting as negative elements of the core loop [76]. With the exception of Clock, which is constitutively expressed, all transcripts oscillate within the SCN, with Per and Cry transcripts peaking at roughly midday and those of their regulator, Bmal1, peaking antiphase to this at around midnight [77]. Core and accessory gene–protein–gene feedback loops, along with important posttranslational mechanisms, contribute to the time delays needed for a 24-hour cycle [76] and ensure the self-sustaining nature of perpetual molecular clock oscillations.
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2016, Cellular SignallingCitation Excerpt :The SCN synchronize the oscillations of peripheral clocks through the neuronal and humoral signals, thus adapting the key metabolic processes of tissues to perform the appropriate physiological and behavioral activities to match the daily rhythm. Briefly, mammalian circadian clocks utilize the transcriptional–translational loops to generate circadian outputs, e.g. metabolic responses and hormone secretion [139–141]. Transcription factors CLOCK and BMAL1 heterodimerize and activate the transcription of hundreds of circadian genes, including also the CRY and PER genes, the proteins coded by these genes are the repressors of CLOCK/BMAL1 complexes.
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