机构：[a]Department of Interventional Neuroradiology, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China重点科室医技科室研究所放射科放射科北京市神经外科研究所首都医科大学附属天坛医院[b]Department of Neurosurgery, Shandong province Qianfoshan Hospital, Shandong University, Jinan 250014, Shandong, China
Dysregulated microRNAs (miRNAs) have been reported to involve in the pathophysiological process of traumatic brain injury (TBI), and modulate autophagy-related genes (ATGs) expression. Our previous studies showed that neuronal autophagy was activated in the injury hippocampus post-TBI and associated with neurological and cognitive impairments. The present study was designed to investigate the possible role of miR-23b in TBI-induced cognitive impairments. We found the overexpression of miR-23b conferred a better neuronprotective effects after TBI by decreasing lesion volume, alleviating brain edema, inhibiting neuron apoptosis and attenuating long-term neurological deficits, and most interestingly, improving cognitive impairments. To further explore the molecular underlying this neuronprotection, we evaluated autophagic activity and ATG12 expression in the injury hippocampus CA1 region. The results identified that miR-23b directly targeted to the 3'UTR region of ATG12 mRNA to suppress the activation of neuronal autophagy by a dual-luciferase reporter system. Notably, overexpression of ATG12 abrogated the neuronprotective effects of miR-23b on TBI-induced neurological and cognitive impairments. Taken together, these date revealed inhibition of ATG12-mediated autophagic activity by miR-23b overexpression might be involve in cognitive improvement after TBI, indicating that miR-23b might be a potential therapeutic target for TBI. (C) 2016 Published by Elsevier B.V.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81171078]; China Postdoctoral Science FoundationChina Postdoctoral Science Foundation [2015M580117]; Beijing Postdoctoral Research FoundationChina Postdoctoral Science Foundation [2015ZZ-49, 2016ZZ-38]
第一作者机构：[a]Department of Interventional Neuroradiology, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China
通讯作者：
通讯机构：[b]Department of Neurosurgery, Shandong province Qianfoshan Hospital, Shandong University, Jinan 250014, Shandong, China[*1]Department of Neurosurgery, Shandong provinceQianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan 250014, Shan-dong, China.
推荐引用方式(GB/T 7714)：
Liqian Sun,Aihua Liu,Jingbo Zhang,et al.miR-23b improves cognitive impairments in traumatic brain injury by targeting ATG12-mediated neuronal autophagy[J].BEHAVIOURAL BRAIN RESEARCH.2018,340:126-136.doi:10.1016/j.bbr.2016.09.020.
