Varenicline improved laparotomy-induced cognitive impairment by restoring mitophagy in aged mice

• DOI: 10.1016/j.ejphar.2021.174524
• Publication Date: 2021-09-27T05:11:30Z
• Authors: Jianan Wang; Shoufeng Zhu; Wenping Lu; Ao Li; Yuqi Zhou; Yihuan Chen; Ming Chen; Cheng Qian; Xianwen Hu; Ye Zhang; Chunxia Huang
• Keywords: Postoperative cognitive dysfunction; Cognitive Decline

Growing incidence of postoperative cognitive dysfunction (POCD) in the elderly populations after major surgery challenges us to provide stable and effective treatments. Mitochondria is essential pathogenesis aging neurodegenerative diseases. It hypothesized that varenicline improves impairment through restoring mitophagy tau phosphorylation. Wild type C57BL/6 mice (male, 18-month-old) were subjected laparotomy with or without chronic administration. Postoperative cognition anxiety determined by Morris water maze elevated plus tests. Meanwhile, oxidative stress, mitochondria function, phosphorylation, as well correlation PKR STAT3 characterized. In aged following laparotomy, persistent spatial learning memory indicated longer escape latency less crossing frequency target quadrant. Laparotomy also induced responses deficits. After 14 days, significant ROS accumulation smaller impaired function presented hippocampus. Simultaneously, there abundant neuronal apoptosis translocation phosphorylation mitochondria. Enhanced down regulated ChAT activity distributed laparotomy. signaling was activated required for subcellular activation brain. administration (1 mg/kg/day), dysfunction, hippocampal fragile improved. Our results highlight caused autophagy dysregulation. PKR/STAT3 maybe potential mechanism, perioperative treatment could be an efficient therapeutic strategy POCD.