title: miR-23b improves cognitive impairments in traumatic brain injury by targeting ATG12-mediated neuronal autophagy.
abstract: 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.
authors.affiliation: Department of Interventional Neuroradiology, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Liqian
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Interventional Neuroradiology, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Liu
authors.affiliation: Department of Interventional Neuroradiology, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Jingbo
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Interventional Neuroradiology, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Ji
authors.affiliation: Department of Interventional Neuroradiology, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Youxiang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Interventional Neuroradiology, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Xinjian
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Interventional Neuroradiology, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Zhongxue
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, Shandong province Qianfoshan Hospital, Shandong University, Jinan 250014, Shandong, China. Electronic address: slq20000@126.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Guo
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D000071192:Autophagy-Related Protein 12 / Q000378:metabolism*; D001929:Brain Edema / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D000070642:Brain Injuries, Traumatic / Q000378:metabolism* / Q000473:pathology / Q000523:psychology* / Q000628:therapy; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D060825:Cognitive Dysfunction / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000066829:Neuroprotection / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D055815:Young Adult
chemical_list: D000071192:Autophagy-Related Protein 12; C552430:MIRN23a microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger
keywords: ATG12; Autophagy; Cognitive impairments; Traumatic brain injury; miR-23b