Investigation of the relationship between methylation of circadian genes and anxiety

Objective: The role of CRY2 and PER3 gene mutations in circadian rhythm disorders and anxiety is recognized, yet there's limited knowledge concerning their DNA methylation patterns influenced by environmental factors. This study aspires to shed light on the connection between the methylation status of CRY2 and PER3 genes and anxiety. Materials and Methods: In this study, a circadian rhythm disorder protocol (6 hours light/18 hours dark) was applied to Wistar Albino rats for 21 days, and a rodent restrainer box was used to induce immobility. At the end of the experiment, anxiety and depression levels were evaluated using the Elevated Plus Maze, Forced Swim Test, and Light-Dark Box tests. The methylation percentage of CRY2 and PER3 genes was determined by real-time polymerase chain reaction (PCR) on DNA obtained from brain tissue samples. Results: Our analyses revealed that in rats subjected to circadian rhythm disorder and restraint stres for 21 days, the CpG methylation levels of CRY2 and PER3 genes increased by 1.6 and 1.4 times, respectively, compared to the control group. Conclusion: Our findings underscore the significance of the methylation levels of CRY2 and PER3 genes in anxiety conditions. In rats subjected to circadian rhythm disorder and restraint type stress, the methylation levels of these genes were markedly higher than those of the control group. This suggests the possibility of using the CpG methylation levels of CRY2 and PER3 genes as potential biomarkers. KEYWORDS: CRY2, PER3, Anxiety, Methylation, Circadian Rhythm