Suppression of microRNA-9-5p rescues learning and memory in chronic cerebral hypoperfusion rats model

// Na Wei 1, 2, 3, * , Kai Zheng 4, * , Rui Xue 5 , Sheng-Li Ma 6 , Hua-Yan Ren 1, 2, 3 , Hui-Fen Huang 1, 2, 3 , Wei-Wei Wang 1, 2, 3 , Jing-Jing Xu 1, 2, 3 and Kui-Sheng Chen 1, 2, 3 1 Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450002, People’s Republic of China 2 Henan Key Laboratory of Tumor Pathology, Zhengzhou 450002, People’s Republic of China 3 Department of Pathology, School of Basic Medicine, Zhengzhou University, Zhengzhou 450002, People’s Republic of China 4 Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China 5 Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450002, People’s Republic of China 6 Department of Emergency, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450002, People’s Republic of China * These authors have contributed equally to this work Correspondence to: Jing-Jing Xu, email: xujingjing_1982@163.com Kui-Sheng Chen, email: kuishengchen@zzu.edu.cn Keywords: miR-9-5p; memory; chronic cerebral hypoperfusion; long-term potentiation Received: May 12, 2017     Accepted: August 17, 2017     Published: November 11, 2017 ABSTRACT Chronic cerebral hypoperfusion has been associated with cognitive impairment in dementias, such as Alzheimer’s disease (AD) and vascular disease (VaD), the two most common neurodegenerative diseases in aged people. However, the effective therapeutic approaches for both AD and VaD are still missing. MicroRNAs (miRNAs) are small non-coding RNAs that play important roles in the epigenetic regulation in many neurological disorders; the critical roles of miRNAderegulation had been implicated in both AD and VaD. In the current study, we reported that miR-9-5p is elevated in the serum and cerebrospinalfluid of patientswith VaD. The miR-9-5p wasalso increased in both the hippocampus and cortex of rats with 2-vessel occlusionsurgery. Furthermore, application ofmiR-9-5p antagomirs attenuated the memory impairments in rats with 2-vessel occlusion surgery both in the Morris water maze and inhibitory avoidance step-down tasks. Furthermore, miR-9-5p antagomirs reducedthe inhibition oflong-term potentiation and loss of dendritic spines in chronic cerebral hypoperfusionrats. Additionally, the cholinergic neuronal function was rescued by miR-9-5p antagomirs, as well as the neuronal loss and the oxidative stress. We concluded that miR-9-5p inhibition may be a potential therapeutic target for the memory impairments caused by chronic cerebral hypoperfusion.