P2X7 receptor inhibition prevents atrial fibrillation in rodent models of depression

• DOI: 10.1093/europace/euae022
• Publication Date: 2024-01-23T20:19:17Z
• Authors: Tianxin Ye; Yunping Zhou; Jinxiu Yang; Fangcong Yu; Zhuonan Song; Jiaran Shi; Longbo Wang; Zhouqing Huang; Bo Yang; Xingxiang Wang
• Keywords: Depression

Abstract Aims Depression, the most prevalent psychiatric disorder, is associated with occurrence and development of atrial fibrillation (AF). P2X7 receptor (P2X7R) activation participates in depression, but little attention has been given to its role AF. This study was investigate effects P2X7R on AF depression models. Methods results Lipopolysaccharide (LPS) chronic unpredictable stress (CUS) were carried out induce rodents. Behavioural assessments, electrophysiological parameters, electrocardiogram (ECG) western blot, histology performed. Atrial inducibility increased both LPS- CUS-induced along up-regulation atria. CUS facilitated fibrosis. reduced heart rate variability (HRV) expression TH GAP43, representing autonomic dysfunction. Down-regulation Nav1.5, Cav1.2, Kv1.5, Kv4.3, Cx40, Cx43 indicated abnormalities ion channels. In addition, levels TLR4, P65, P-P65, NLRP3, ASC, caspase-1, IL-1β elevated Pharmacological inhibitor (Brilliant Blue G, BBG) or genetic deficiency significantly mitigated depressive-like behaviours; ameliorated deterioration dysfunction; improved channel fibrosis; prevented NLRP3 inflammasome pathophysiological process Conclusion LPS induces promotes P2X7R-dependent inflammasome, whereas pharmacological inhibition prevents remodelling without interrupting normal physiological functions. Our point as an important factor pathology depression.