title: Replenishment of microRNA-188-5p restores the synaptic and cognitive deficits in 5XFAD Mouse Model of Alzheimer's Disease.
abstract: MicroRNAs have emerged as key factors in development, neurogenesis and synaptic functions in the central nervous system. In the present study, we investigated a pathophysiological significance of microRNA-188-5p (miR-188-5p) in Alzheimer's disease (AD). We found that oligomeric Aβ1-42treatment diminished miR-188-5p expression in primary hippocampal neuron cultures and that miR-188-5p rescued the Aβ1-42-mediated synapse elimination and synaptic dysfunctions. Moreover, the impairments in cognitive function and synaptic transmission observed in 7-month-old five familial AD (5XFAD) transgenic mice, were ameliorated via viral-mediated expression of miR-188-5p. miR-188-5p expression was down-regulated in the brain tissues from AD patients and 5XFAD mice. The addition of miR-188-5p rescued the reduction in dendritic spine density in the primary hippocampal neurons treated with oligomeric Aβ1-42and cultured from 5XFAD mice. The reduction in the frequency of mEPSCs was also restored by addition of miR-188-5p. The impairments in basal fEPSPs and cognition observed in 7-month-old 5XFAD mice were ameliorated via the viral-mediated expression of miR-188-5p in the hippocampus. Furthermore, we found that miR-188 expression is CREB-dependent. Taken together, our results suggest that dysregulation of miR-188-5p expression contributes to the pathogenesis of AD by inducing synaptic dysfunction and cognitive deficits associated with Aβ-mediated pathophysiology in the disease.
authors.affiliation: Department of Pharmacology, College of Medicine, Seoul National University, Seoul, 110-799, Republic of Korea.
authors.forename: Kihwan
authors.initials: K
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, College of Medicine, Seoul National University, Seoul, 110-799, Republic of Korea.
authors.forename: Hyunju
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Life Science, POSTECH, Pohang, Gyeongbuk, 790-784, Republic of Korea.
authors.forename: Kyongman
authors.initials: K
authors.lastname: An
authors.affiliation: Department of Life Science, POSTECH, Pohang, Gyeongbuk, 790-784, Republic of Korea.
authors.forename: Oh-Bin
authors.initials: OB
authors.lastname: Kwon
authors.affiliation: Department of Life Science, POSTECH, Pohang, Gyeongbuk, 790-784, Republic of Korea.
authors.forename: Sungjun
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Physiology, College of Medicine, Seoul National University, Seoul, 110-799, Republic of Korea.
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Cha
authors.affiliation: Department of Physiology, College of Medicine, Seoul National University, Seoul, 110-799, Republic of Korea.
authors.forename: Myoung-Hwan
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Department of Life Science, POSTECH, Pohang, Gyeongbuk, 790-784, Republic of Korea.
authors.forename: Yoontae
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of Life Science, POSTECH, Pohang, Gyeongbuk, 790-784, Republic of Korea.
authors.forename: Joung-Hun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology (LINE), Faculty of Medicine and Dentistry, University of Bristol, Whitson Street, Bristol BS1 3NY, UK.|Centre for Synaptic Plasticity, School of Clinical Sciences, Faculty of Medicine and Dentistry, University of Bristol, Whitson Street, Bristol BS1 3NY, UK.
authors.forename: Kwangwook
authors.initials: K
authors.lastname: Cho
authors.affiliation: Department of Pharmacology, College of Medicine, Seoul National University, Seoul, 110-799, Republic of Korea.|Seoul National University Bundang Hospital, College of Medicine, Seoul National University, Seongnam, Gyeonggi, 463-707, Republic of Korea.
authors.forename: Hye-Sun
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D060825:Cognitive Dysfunction / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000096:biosynthesis / Q000235:genetics; D013569:Synapses / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D016229:Amyloid beta-Peptides; C000594549:MIRN188 microRNA, mouse; D035683:MicroRNAs; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)