LPM570065 ameliorates anxiety-like and depressive-like behaviors in CUMS rats through regulating DNA methylation in hippocampus

Objective: In this study, we aimed to analyze the effects and underlying mechanisms of LPM570065 on behavioral phenotypes in rats with generalized anxiety disorder (GAD).Methods: The chronic unpredictable mild stress (CUMS) were used observe results LPM570065. Total 72 male Sprague Dawley divided into control, vehicle (0.5% CMC-Na), (32 mg/kg) diazepam (3 groups, 12 each group. Anxiety-like behaviors observed by elevated zero maze test novelty-suppressed feeding test. Depressive-like detected forced swimming DNA methylation hippocampi measured reduced representation bisulfite sequencing (RRBS). rats, expressions methyltransferase (DNMT) 1 DNMT3a proteins western blot, density dendritic spines was Golgi staining.Results: Compared control group, weights obviously decreased (p < 0.001) showed anxiety-like depressive-like significantly increased improved RRBS that there 49964 promoters hypermethylation treatment contrasted rats. addition, these enriched signal transduction immune function. Furthermore, DNMT1 decreased, compared rats.Conclusions: ameliorates CUMS its mechanism is possible associated downregulating hippocampus.