title: MiR-214-3p attenuates cognition defects via the inhibition of autophagy in SAMP8 mouse model of sporadic Alzheimer's disease.
abstract: The autophagy process is the major cellular degradation pathway for long-lived proteins and organelles. Dysfunction of autophagy may lead to several neurodegenerative disorders. However, the regulation and function of autophagy in sporadic Alzheimer's disease (SAD) remain unclear. In this study, we established SAMP8 mouse as a suitable SAD model and performed microarray profiling to identify miR-214-3p as a SAD associated microRNA that was downregulated in hippocampal neurons of SAMP8 mice upon the induction of autophagy. Furthermore, decreased miR-214-3p level was detected in cerebrospinal fluid from SAD patients. Overexpression of miR-214-3p in primary neurons from SAMP8 mice inhibited autophagy, demonstrated by decreased levels of LC3βII and Beclin1, and reduced number of GFP-LC3-positive autophagosome vesicles, and led to increased viability and decreased caspase-mediated apoptosis. Conversely, antagomiR-214-3p promoted autophagy and apoptosis in neurons from SAMP8 mice. Mechanistically, miR-214-3p negatively regulated Atg12 expression by targeting the 3'-untranslated region of Atg12. Treatment of SAMP8 mice with miR-214-3p attenuated neuronal apoptosis and improved behavioral performance. Taken together, these results suggest that miR-214-3p suppresses autophagy and alleviates hippocampal neuron apoptosis, which indicates that miR-214-3p represents a new potential neuroprotective factor for SAD.
authors.affiliation: Department of Neurology of Weifang People's Hospital, Weifang 261041, Shandong, PR China.
authors.forename: Yueqi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Medical Laboratory of Beijing Children's Hospital, Capital Medical University, Beijing 100053, PR China.
authors.forename: Qiliang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Clinical Laboratory of Xuanwu Hospital, Capital Medical University, Beijing 100053, PR China.
authors.forename: Chengeng
authors.initials: C
authors.lastname: Liu
authors.affiliation: Clinical Laboratory of Xuanwu Hospital, Capital Medical University, Beijing 100053, PR China.
authors.forename: Shichao
authors.initials: S
authors.lastname: Gao
authors.affiliation: Clinical Laboratory of Xuanwu Hospital, Capital Medical University, Beijing 100053, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Ping
authors.affiliation: Clinical Laboratory of Xuanwu Hospital, Capital Medical University, Beijing 100053, PR China.
authors.forename: Jinling
authors.initials: J
authors.lastname: Wang
authors.affiliation: Clinical Laboratory of Xuanwu Hospital, Capital Medical University, Beijing 100053, PR China. Electronic address: peichangwang@yahoo.com.
authors.forename: Peichang
authors.initials: P
authors.lastname: Wang
mesh_terms: D000368:Aged; D000375:Aging / Q000235:genetics; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000150:complications* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003072:Cognition Disorders / Q000209:etiology* / Q000628:therapy*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D004622:Embryo, Mammalian; D005260:Female; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008817:Mice, Mutant Strains; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009841:Oligonucleotides / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; C480860:Map1lc3b protein, mouse; D035683:MicroRNAs; D008869:Microtubule-Associated Proteins; C534781:Mirn214 microRNA, mouse; D009841:Oligonucleotides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)
keywords: Apoptosis; Atg12; Autophagy; Sporadic Alzheimer’s disease; miR-214-3p