Neuropsychiatric Disease and Treatment (Jul 2023)
Ru360 Alleviates Postoperative Cognitive Dysfunction in Aged Mice by Inhibiting MCU-Mediated Mitochondrial Dysfunction
Abstract
Xiaoxiao Xu, Bin Zhou, Jun Liu, Qianli Ma, Tengyu Zhang, Xiang Wu The First Hospital of Ningbo University, Ningbo, 315211, People’s Republic of ChinaCorrespondence: Xiang Wu, The First Hospital of Ningbo University, Ningbo, 315211, People’s Republic of China, Email [email protected]: Ru360, a selective inhibitor of mitochondrial calcium uptake, maintains mitochondrial calcium homeostasis. To evaluate whether mitochondrial calcium uniporter (MCU)-mediated mitochondrial function is associated with the pathological process of Postoperative cognitive dysfunction (POCD), elucidate its relationship with neuroinflammation, and observe whether the relevant pathological process can be improved with Ru360.Methods: Aged mice underwent experimental open abdominal surgery after anesthesia. Open field tests, Novel object recognition tests and Y Maze Tests were used to conduct behavioral experiments. The reactive oxygen species (ROS) content, the levels of inflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), intra-mitochondrial calcium, mitochondrial membrane potential (MMP) and the activity of antioxidant superoxide dismutase (SOD) in the hippocampus of mice were detected using kits. The expression of proteins was detected using Western blot.Results: After treatment with Ru360, MCU-mediated mitochondrial dysfunction was inhibited, neuroinflammation was reduced, and the learning ability of the mice was improved after surgery.Conclusion: Our study demonstrated that mitochondrial function plays a crucial role in the pathology of POCD, and using Ru360 to improve mitochondrial function may be a new and necessary direction for the treatment of POCD.Keywords: postoperative cognitive dysfunction, mitochondria, Ru360, mitochondrial calcium uniporter, neuroinflammation
