Retinoic Acid Receptor Is a Novel Therapeutic Target for Postoperative Cognitive Dysfunction
Yongjie Bao,
Wenni Rong,
An Zhu,
Yuan Chen,
Huiyue Chen,
Yirui Hong,
Jingyang Le,
Qiyao Wang,
C. Benjamin Naman,
Zhipeng Xu,
Lin Liu,
Wei Cui,
Xiang Wu
Affiliations
Yongjie Bao
Department of Anesthesiology, The First Affiliated Hospital of Ningbo University, Ningbo 315010, China
Wenni Rong
Translational Medicine Center of Pain, Emotion and Cognition, Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, China
An Zhu
Translational Medicine Center of Pain, Emotion and Cognition, Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, China
Yuan Chen
Translational Medicine Center of Pain, Emotion and Cognition, Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, China
Huiyue Chen
Translational Medicine Center of Pain, Emotion and Cognition, Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, China
Yirui Hong
Translational Medicine Center of Pain, Emotion and Cognition, Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, China
Jingyang Le
Department of Anesthesiology, The First Affiliated Hospital of Ningbo University, Ningbo 315010, China
Qiyao Wang
Department of Anesthesiology, The First Affiliated Hospital of Ningbo University, Ningbo 315010, China
C. Benjamin Naman
Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Research Center, Ningbo University, Ningbo 315211, China
Zhipeng Xu
Department of Anesthesiology, The First Affiliated Hospital of Ningbo University, Ningbo 315010, China
Lin Liu
Department of Anesthesiology, The First Affiliated Hospital of Ningbo University, Ningbo 315010, China
Wei Cui
Department of Anesthesiology, The First Affiliated Hospital of Ningbo University, Ningbo 315010, China
Xiang Wu
Department of Anesthesiology, The First Affiliated Hospital of Ningbo University, Ningbo 315010, China
Postoperative cognitive dysfunction (POCD) is a clinical syndrome characterizing by cognitive impairments in the elderly after surgery. There is limited effective treatment available or clear pathological mechanisms known for this syndrome. In this study, a Connectivity Map (CMap) bioinformatics model of POCD was established by using differently expressed landmark genes in the serum samples of POCD and non-POCD patients from the only human transcriptome study. The predictability and reliability of this model were further supported by the positive CMap scores of known POCD inducers and the negative CMap scores of anti-POCD drug candidates. Most retinoic acid receptor (RAR) agonists were negatively associated with POCD in this CMap model, suggesting that RAR might be a novel target for POCD. Most importantly, acitretin, a clinically used RAR agonist, significantly inhibited surgery-induced cognitive impairments and prevented the reduction in RARα and RARα-target genes in the hippocampal regions of aged mice. The study denotes a reliable CMap bioinformatics model of POCD for future use and establishes that RAR is a novel therapeutic target for treating this clinical syndrome.
