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

Abstract

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.

• Authors: Xue-Lei Yin, Jing-Cao Li, Rui Xue, Shuo Li, Yang Zhang, Hua-Jin Dong, Ying Li, Heng-Lin Wang, You-Zhi Zhang
• Journal: Experimental neurology (Exp Neurol) Vol. 354 Pg. 114086 (08 2022) ISSN: 1090-2430 [Electronic] United States
• PMID: 35460759 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022. Published by Elsevier Inc.

Chemical References

• Glycogen Synthase Kinase 3 beta
• Melatonin
• Propofol

Topics

• Animals
• Circadian Rhythm (drug effects)
• Glycogen Synthase Kinase 3 beta
• Humans
• Melatonin (pharmacology)
• Propofol (pharmacology)
• Rats
• Sleep
• Sleep Wake Disorders (chemically induced, prevention & control)