Circadian Rhythm Sleep Disorder: Genetic and Environmental Factors

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DNA methylation and transcription onset in the brain

Aim: The goal of this study was to test the state of methylation of transcription start positions in DNA that are actively involved in transcription. Materials &amp; methods: We used sequential ChIP-bisulfite-sequencing with an antibody to RNpolII-PS5 to map the state of methylation of actively transcribing transcription start sites (TSS). Results: TSS that RNApolII-PS5 physically bind to, are ubiquitously unmethylated. TSS that appear to be both heavily methylated and transcriptionally active are truly a mixture of unmethylated TSS with bound RNApolII-PS5 in some nuclei and unbound methylated TSS in other nuclei. Conclusion: TSS DNA methylation is universally inconsistent with transcription onset and could therefore serve as a digital count of the fraction of nuclei with methylation-silenced TSS. </jats:p

Rapid fast-delta decay following prolonged wakefulness marks a phase of wake-inertia in NREM sleep

Sleep-wake driven changes in non-rapid-eye-movement sleep (NREM) sleep (NREMS) EEG delta (delta-)power are widely used as proxy for a sleep homeostatic process. Here, we noted frequency increases in delta-waves in sleep-deprived mice, prompting us to re-evaluate how slow-wave characteristics relate to prior sleep-wake history. We identified two classes of delta-waves; one responding to sleep deprivation with high initial power and fast, discontinuous decay during recovery sleep (delta2) and another unrelated to time-spent-awake with slow, linear decay (delta1). Reanalysis of previously published datasets demonstrates that delta-band heterogeneity after sleep deprivation is also present in human subjects. Similar to sleep deprivation, silencing of centromedial thalamus neurons boosted subsequent delta2-waves, specifically. delta2-dynamics paralleled that of temperature, muscle tone, heart rate, and neuronal ON-/OFF-state lengths, all reverting to characteristic NREMS levels within the first recovery hour. Thus, prolonged waking seems to necessitate a physiological recalibration before typical NREMS can be reinstated

Comprehensive Mapping of Regional Expression of the Clock Protein PERIOD2 in Rat Forebrain across the 24-h Day

In mammals, a light-entrainable clock located in the suprachiasmatic nucleus (SCN) regulates circadian rhythms by synchronizing oscillators throughout the brain and body. Notably, the nature of the relation between the SCN clock and subordinate oscillators in the rest of the brain is not well defined. We performed a high temporal resolution analysis of the expression of the circadian clock protein PERIOD2 (PER2) in the rat forebrain to characterize the distribution, amplitude and phase of PER2 rhythms across different regions. Eighty-four LEW/Crl male rats were entrained to a 12-h: 12-h light/dark cycle, and subsequently perfused every 30 min across the 24-h day for a total of 48 time-points. PER2 expression was assessed with immunohistochemistry and analyzed using automated cell counts. We report the presence of PER2 expression in 20 forebrain areas important for a wide range of motivated and appetitive behaviors including the SCN, bed nucleus, and several regions of the amygdala, hippocampus, striatum, and cortex. Eighteen areas displayed significant PER2 rhythms, which peaked at different times of day. Our data demonstrate a previously uncharacterized regional distribution of rhythms of a clock protein expression in the brain that provides a sound basis for future studies of circadian clock function in animal models of disease