Melatonin upregulates BMAL1 to attenuate chronic sleep deprivation‐related cognitive impairment by alleviating oxidative stress

• Published in: Brain and behavior Vol. 13; no. 1; pp. e2836 - n/a
• Main Authors: Hu, Yujie, Yin, Jierong, Yang, Guoshuai
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.01.2023; John Wiley and Sons Inc; Wiley
• Subjects: Animal cognition; Antibodies; Antigens; ARNTL Transcription Factors - genetics; ARNTL Transcription Factors - metabolism; ARNTL Transcription Factors - pharmacology; bcl-2-Associated X Protein - metabolism; BMAL1; Circadian rhythm; Cognitive ability; Cognitive Dysfunction - complications; Genes; Humans; Interleukin-6; Melatonin; Melatonin - pharmacology; Melatonin - therapeutic use; Original; Oxidative Stress; Proteins; Sleep deprivation; Sleep Deprivation - complications; Sleep Deprivation - drug therapy; Superoxide Dismutase - metabolism; Tumor Necrosis Factor-alpha - metabolism; China; sleep deprivation; melatonin; BMAL1; oxidative stress
• DOI: 10.1002/brb3.2836
• ISSN: 2162-3279

Purpose To investigate the mechanism underlying the regulatory effect of melatonin on chronic sleep deprivation‐related cognitive impairment. Methods Chronic sleep deprivation (CSD) model was established using the MMPM method. After the model was established, melatonin receptor agonist and inhibitor were given, respectively. Water maze was conducted to record the escape latency and the duration of crossing the platform of space exploration. The concentration of TNF‐α, IL‐6, MDA, and SOD was measured by ELISA. Immunofluorescence was used to determine the expression level of CD86 and CD206, while the mRNA expression of Bax, Bcl‐2, P65, IκB, and BMAL1 was detected by qPCR. Western blotting assay was utilized to determine the protein expression of Bax, Bcl‐2, P65, p‐P65, IκB, p‐I κB, and BMAL1. Results Compared with the control, the escape latency was greatly increased on the second and third day, accompanied by the increased expression of TNF‐α, IL‐6, MDA, and SOD in serum. Furthermore, dramatically upregulated Bax, Bcl‐2, P65, IκB, and CD86 were observed in the model group, accompanied by the declined expression level of BMAL1 and CD206. Compared with the model group, the escape latency was declined, the concentration of TNF‐α, IL‐6, MDA, and SOD was decreased, the expression level of Bax, Bcl‐2, P65, IκB, and CD86 was declined, and the level of BMAL1 and CD206 was promoted by the treatment of the melatonin agonist, while the opposite results were observed under the treatment of the melatonin inhibitor. Conclusion Melatonin upregulates BMAL1 to attenuate chronic sleep deprivation‐related cognitive impairment by alleviating oxidative stress. The present study aims to investigate the effect of melatonin on cognitive dysfunction in sleep‐deprived rats and the underlying mechanism. We speculated that melatonin upregulated BMAL1 to attenuate chronic sleep deprivation related cognitive impairment by allevaiting oxidative stress.