Melatonin attenuates chronic sleep deprivation‐induced cognitive deficits and HDAC3‐Bmal1/clock interruption

• Published in: CNS neuroscience & therapeutics Vol. 30; no. 3; pp. e14474 - n/a
• Main Authors: Hu, Yujie, Lv, Yefan, Long, Xiaoyan, Yang, Guoshuai, Zhou, Jinxia
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.03.2024; John Wiley and Sons Inc
• Subjects: Animal cognition; Animal models; Animals; Bmal1; BMAL1 protein; Circadian rhythm; Circadian Rhythm - genetics; Circadian rhythms; clock; Cognition; Cognitive ability; Cognitive Dysfunction; Ethanol; Eye Diseases, Hereditary; Eye movements; Genetic Diseases, X-Linked; HDAC3; Hippocampus; Laboratory animals; Latency; Light; Male; Melatonin; Melatonin - pharmacology; Melatonin - therapeutic use; Memory; mRNA; Myopia; Night Blindness; Original; Peripheral blood; Physiology; Rats; Rats, Sprague-Dawley; REM sleep; Sleep deprivation; Sleep Deprivation - complications; Sleep Deprivation - drug therapy; Spatial discrimination learning; Spatial memory; Therapeutic targets; China; sleep deprivation; HDAC3; cognition; circadian rhythm; clock; melatonin; Bmal1
• ISSN: 1755-5930; 1755-5949
• DOI: 10.1111/cns.14474

Background and Aims Sleep is predicted as a key modulator of cognition, but the underlying mechanisms are poorly understood. In this study, we investigated the effects of melatonin on chronic rapid eye movement sleep deprivation (CRSD)‐induced cognitive impairment and circadian dysfunction in rat models. Methods Thirty‐six Sprague‐Dawley male rats were divided into three groups: CRSD with saline treatment, CRSD with chronic melatonin injection (20 mg/kg/day), and non‐sleep‐deprived control. The cognitive behavioral tests as well as the expression of clocks and HDAC3 were evaluated in all groups. Results CRSD significantly reduced recognition index in novel object location, increased escape latency and distance traveling in Morris water maze while melatonin treatment attenuated CRSD‐induced hippocampal‐dependent spatial learning and memory deficits. Furthermore, the mRNAs of brain and muscle aryl hydrocarbon receptor nuclear translocator‐like 1(Bmal1) and circadian locomotor output cycles kaput (Clock) were globally down‐regulated by CRSD with constant intrinsic oscillation in both hippocampus and peripheral blood. The protein levels of hippocampal Bmal1, Clock, and HDAC3 were also remarkably down‐regulated following CRSD. Melatonin treatment reversed CRSD‐induced alterations of Bmal1/Clock and HDAC3 on both mRNA levels and protein levels. Conclusions Our data indicate that melatonin treatment attenuates CRSD‐induced cognitive impairment via regulating HDAC3‐Bmal1/Clock interaction. These findings explore a broader understanding of the relationship between sleep and cognition and provide a potential new therapeutic target for cognitive impairment. Melatonin treatment attenuates chronic rapid eye movement sleep deprivation‐induced hippocampal‐dependent spatial learning and memory deficits via regulating HDAC3‐Bmal1/Clock interaction.