The effect of AdipoRon on oxidative stress and the expression of genes related to circadian rhythm in the hypothalamus of mice in the chronic sleep restriction model

Abstract

Circadian rhythm, which regulates 24-hour cycles of biological activities, plays a key role in maintaining the body's physiological balance. Disruption of this rhythm due to chronic sleep deprivation can lead to serious consequences, including increased oxidative stress and decreased cognitive and metabolic functions. The aim of this study was to investigate the effect of AdipoRon (AR), as an adiponectin receptor agonist, on the expression of genes related to circadian rhythm, oxidative stress, and Sirt-1 protein expression in mice subjected to chronic sleep restriction. Methods: In this study, 40 adult male Swiss mice weighing 25±5 g were used. The mice were randomly divided into four groups of ten animals, including: control group, chronic sleep restriction (CSR) group, CSR+melatonin group, and CSR+AR group. Sleep restriction was induced using the Multiple Platform Induction device for 21 consecutive days. AR and melatonin treatment were administered intranasally at doses of 10 and 40 μg, respectively, for 21 days. After the end of the treatments, oxidative stress indices including malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), and total antioxidant capacity (TAC) and the expression of circadian rhythm-related genes including Bmal1, Clock, Per1, and Cry1 were measured using Real-Time PCR. Also, Sirt-1 protein expression was examined by Western blotting in the hypothalamus. Results: The results of this study showed that the induction of chronic sleep restriction caused a significant decrease in the expression of Bmal1, Clock, Per1, and Cry1 genes and an increase in MDA levels and a decrease in the activity of SOD, GPx, and TAC enzymes in the hypothalamus. However, AR treatment significantly corrected these changes and restored gene expression and antioxidant activity to levels close to the control group. Also, Sirt-1 protein expression was increased in the CSR+AR group compared to the CSR group.