title: MicroRNA-181c Ameliorates Cognitive Impairment Induced by Chronic Cerebral Hypoperfusion in Rats.
abstract: Chronic cerebral hypoperfusion (CCH) characterized by global cerebral ischemia is an important risk factor contributing to the development of dementia. MicroRNAs (miRNAs) play important roles in the cellular adaptation to long-term ischemia/hypoxia by turning off or on the expression of target genes. MiR-181c is widely expressed in the nervous system, and tripartite motif 2 (TRIM2) is one of its target genes. In this work, we had identified that progressive spatial memory deficiency was induced in the bilateral common carotid artery occlusion (2-VO) rat models. Meanwhile, inhibition of miR-181c expression and upregulation of TRIM2 in the hippocampus of 2-VO rats were found accompanying with reduction in the dendritic branching and dendrite spine density of the hippocampal neurons. Viral vector-mediated miR-181c delivery might improve the cognitive deficiency via TRIM2 on neurofilament light (NF-L) ubiquitination resulting in remodeling of the hippocampal neurons as well as increase in N-methyl-D-aspartate receptor 1 (NR1) subunit cell surface expression. Meanwhile, miR-181c might rescue the cellular activity from ischemia/hypoxia. These results indicated a novel miRNA-mediated mechanism involving miR-181c and TRIM2 in the cognitive impairment induced by CCH and provided a rationale for the development of miRNA-based strategies for prevention of dementia.
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Capital Medical University, 10 Xi Tou Tiao, You An Men street, Beijing, 100069, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Fang
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Capital Medical University, 10 Xi Tou Tiao, You An Men street, Beijing, 100069, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Capital Medical University, 10 Xi Tou Tiao, You An Men street, Beijing, 100069, China.
authors.forename: Guowen
authors.initials: G
authors.lastname: Min
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Capital Medical University, 10 Xi Tou Tiao, You An Men street, Beijing, 100069, China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Capital Medical University, 10 Xi Tou Tiao, You An Men street, Beijing, 100069, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cui
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Capital Medical University, 10 Xi Tou Tiao, You An Men street, Beijing, 100069, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Capital Medical University, 10 Xi Tou Tiao, You An Men street, Beijing, 100069, China. liliang8698@yeah.net.
authors.forename: Liang
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D016893:Carotid Stenosis / Q000150:complications / Q000378:metabolism*; D002470:Cell Survival / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D002908:Chronic Disease; D060825:Cognitive Dysfunction / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D006624:Hippocampus / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis*; D009687:Nuclear Proteins / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C540193:MIrn181 microRNA, human; D035683:MicroRNAs; C400022:NARF protein, human; D009687:Nuclear Proteins
keywords: Chronic cerebral hypoperfusion; Cognition; MicroRNA-181c; Rat; Tripartite motif 2; Ubiquitination