Journal Articles

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    General Anaesthesia Shifts the Murine Circadian Clock in a Time-Dependant Fashion
    (MDPI (Basel, Switzerland), 2021-01-26) Ludin NM; Orts-Sebastian A; Cheeseman JF; Chong J; Merry AF; Cumin D; Yamazaki S; Pawley MDM; Warman GR
    Following general anaesthesia (GA), patients frequently experience sleep disruption and fatigue, which has been hypothesized to result at least in part by GA affecting the circadian clock. Here, we provide the first comprehensive time-dependent analysis of the effects of the commonly administered inhalational anaesthetic, isoflurane, on the murine circadian clock, by analysing its effects on (a) behavioural locomotor rhythms and (b) PER2::LUC expression in the suprachiasmatic nuclei (SCN) of the mouse brain. Behavioural phase shifts elicited by exposure of mice (n = 80) to six hours of GA (2% isoflurane) were determined by recording wheel-running rhythms in constant conditions (DD). Phase shifts in PER2::LUC expression were determined by recording bioluminescence in organotypic SCN slices (n = 38) prior to and following GA exposure (2% isoflurane). Full phase response curves for the effects of GA on behaviour and PER2::LUC rhythms were constructed, which show that the effects of GA are highly time-dependent. Shifts in SCN PER2 expression were much larger than those of behaviour (c. 0.7 h behaviour vs. 7.5 h PER2::LUC). We discuss the implications of this work for understanding how GA affects the clock, and how it may inform the development of chronotherapeutic strategies to reduce GA-induced phase-shifting in patients.
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    The Effects of General Anaesthesia and Light on Behavioural Rhythms and GABAA Receptor Subunit Expression in the Mouse SCN.
    (MDPI (Basel, Switzerland), 2021-09-17) Chong J; Cheeseman JF; Pawley MDM; Kwakowsky A; Warman GR; Cajochen C
    General anaesthesia (GA) is known to affect the circadian clock. However, the mechanisms that underlie GA-induced shifting of the clock are less well understood. Activation of γ-aminobutyric acid (GABA)-type A receptors (GABAAR) in the suprachiasmatic nucleus (SCN) can phase shift the clock and thus GABA and its receptors represent a putative pathway via which GA exerts its effect on the clock. Here, we investigated the concurrent effects of the inhalational anaesthetic, isoflurane, and light, on mouse behavioural locomotor rhythms and on α1, β3, and γ2 GABAAR subunit expression in the SCN of the mouse brain. Behavioural phase shifts elicited by exposure of mice to four hours of GA (2% isoflurane) and light (400 lux) (n = 60) were determined by recording running wheel activity rhythms in constant conditions (DD). Full phase response curves for the effects of GA + light on behavioural rhythms show that phase shifts persist in anaesthetized mice exposed to light. Daily variation was detected in all three GABAAR subunits in LD 12:12. The γ2 subunit expression was significantly increased following GA in DD (compared to light alone) at times of large behavioural phase delays. We conclude that the phase shifting effect of light on the mouse clock is not blocked by GA administration, and that γ2 may potentially be involved in the phase shifting effect of GA on the clock. Further analysis of GABAAR subunit expression in the SCN will be necessary to confirm its role.
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    Social Jetlag and Cardiometabolic Risk in Preadolescent Children
    (Frontiers Media SA, 2021-10-07) Castro N; Diana J; Blackwell J; Faulkner J; Lark S; Skidmore P; Hamlin M; Signal L; Williams MA; Stoner L; Barseghian A
    Objective: Childhood cardiometabolic disease risk (CMD) has been associated with short sleep duration. Its relationship with other aspects of sleep should also be considered, including social jetlag (SJL) which represents the difference between a person's social rhythms and circadian clock. This study investigated whether childhood CMD risk is associated with sleep duration, sleep disturbances, and SJL. Study Design: The observational study included 332 children aged 8-10 years (48.5% female). The three independent variables were sleep duration, sleep disturbances, and SJL. SJL was calculated as the variation in hours between the midpoint of sleep during free (weekend) days and work/school days. Eleven cardiometabolic biomarkers were measured, including central blood pressure, lipids, glycated hemoglobin, arterial wave reflection, and glucose. Underlying CMD risk factors were identified using factor analysis. Results: Four underlying CMD risk factors were identified using factor analysis: blood pressure, cholesterol, vascular health, and carbohydrate metabolism. Neither sleep disturbances nor sleep duration were significantly associated with any of the four CMD factors following adjustments to potential confounders. However, SJL was significantly linked to vascular health (p = 0.027) and cholesterol (p = 0.025). Conclusion: These findings suggest that SJL may be a significant and measurable public health target for offsetting negative CMD trajectories in children. Further studies are required to determine biological plausibility.