Melatonin pretreatment prevents propofol-induced sleep disturbance by modulating circadian rhythm in rats

Apr 23, 2022Experimental neurology

Melatonin before sleep stops propofol from disturbing daily sleep cycles in rats

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Abstract

Prolonged propofol anesthesia significantly impacts circadian rhythm, reducing oscillation amplitude of sleep and related physiological processes within 24 hours.

Circadian rhythm disturbances may occur after general anesthesia, affecting sleep, body temperature, and movement.
Prolonged propofol anesthesia inhibits the expression of circadian factors PER and CRY in the hypothalamus.
Activation of the CAMK-CREB signaling pathway may be involved in the inhibition of these circadian factors.
Post-translational factors such as GSK-3β, SIRT1, and AMPK may also play a role in regulating circadian factors following propofol anesthesia.
Exogenous melatonin pretreatment could restore circadian rhythm by modulating circadian factor expression and reducing excessive melatonin synthesis.

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Postoperative sleep disorder frequently occurs in patients after surgery. Sleep disturbance aggravates pain, anxiety, and delirium, which is an important risk factor for poor recovery. Circadian rhythm disorder induced by general anesthesia plays important role in postoperative sleep disorders. A large number of clinical studies have shown that various forms and duration of general anesthesia can lead to postoperative sleep disorders. In this study, the effect of prolonged propofol anesthesia on biological rhythm was comprehensively evaluated by wireless physiological telemetry system, and the therapeutic effect of exogenous melatonin pretreatment was further investigated. The results showed that prolonged propofol anesthesia had significant impacts on the circadian rhythm of sleep, body temperature, locomotor activity and endogenous melatonin secretion within 24 h following anesthesia, resulting in diminished oscillation amplitude. In hypothalamus, the expression of circadian factor PER and CRY were inhibited by propofol, possibly through activation of CAMK-CREB signaling pathway. Post-translational factors GSK-3β, SIRT1, AMPK were also involved in the regulation of circadian factors after propofol anesthesia. Melatonin pretreatment could restore circadian rhythm process by regulating circadian factor expression through post-translational modulation and prohibit the over-synthesis of melatonin in pineal gland. This study verified the effects of anesthetics on circadian rhythm and further evaluated the potential therapeutic effect of melatonin on postoperative circadian rhythm and sleep disorders.

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Melatonin pretreatment prevents propofol-induced sleep disturbance by modulating circadian rhythm in rats

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