title: MicroRNA-574 is involved in cognitive impairment in 5-month-old APP/PS1 mice through regulation of neuritin.
abstract: Alzheimer's disease (AD) is the most common form of dementia in the elderly. The recent evidence in AD research suggests that alterations in the microRNA (miRNA) could contribute to risk for the disease. However, little is understood about the roles of miRNAs in cognitive impairment of early Alzheimer's disease (AD). Here, we used 5-month-old APP/PS1 mice, which mimic many of the salient features of the early stage of AD pathological process, to further investigate the roles of miRNAs in synaptic loss involved in learning and memory. We used miRNA expression microarrays on RNA extracted from the hippocampus of 5-month-old APP/PS1 mice and wild type mice. Real-time reverse transcription PCR was conducted to verify the candidate miRNAs discovered by microarray analysis. The data showed that miR-574 was increased significantly in the hippocampus of 5-month-old APP/PS1 mice, which were concomitant with that APP/PS1 mice at the same age displayed a significant synaptic loss and cognitive deficits. Bioinformatic analysis predicted that neuritin (Nrn1) mRNA is targeted by miR-574. Overexpression of miR-574 lowers the levels of neuritin and synaptic proteins expression in primary hippocampal neurons damage induced by Aβ25-35. And the expression of miR-574 was also up-regulated in the hippocampal neurons from APP/PS1 mice compared with WT littermates. In contrast, suppression of miR-574 by miR-574 inhibitor significantly results in higher levels of neuritin and synaptic proteins expression. Taken together, miR-574 is involved in cognitive impairment in 5-month-old APP/PS1 mice through regulation of neuritin.
authors.affiliation: Department of Anatomy, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.affiliation: Research & Development of New Drugs, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wei
authors.affiliation: Department of Anatomy, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Anatomy, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
authors.forename: Yunjun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Anatomy, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
authors.forename: Fengyuan
authors.initials: F
authors.lastname: Huang
authors.affiliation: Department of Anatomy, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Anatomy, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
authors.forename: Qiuke
authors.initials: Q
authors.lastname: Hou
authors.affiliation: Department of Anatomy, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
authors.forename: Rudong
authors.initials: R
authors.lastname: Deng
authors.affiliation: Department of Anatomy, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
authors.forename: Jian Hong
authors.initials: JH
authors.lastname: Zhou
authors.affiliation: Department of Anatomy, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
authors.forename: Sai Xia
authors.initials: SX
authors.lastname: Zhang
authors.affiliation: Department of Anatomy, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China. Electronic address: CDF27212@21cn.com.
authors.forename: Dong Feng
authors.initials: DF
authors.lastname: Chen
mesh_terms: D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D003072:Cognition Disorders / Q000209:etiology* / Q000473:pathology*; D004195:Disease Models, Animal; D058851:GPI-Linked Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D046228:Microarray Analysis; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D053764:Presenilin-1 / Q000235:genetics; D013569:Synapses / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D058851:GPI-Linked Proteins; C580862:MIRN574 microRNA, mouse; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; C484377:Nrn1 protein, mouse; D010446:Peptide Fragments; D053764:Presenilin-1; D016708:Synaptophysin; C075222:amyloid beta-protein (1-42); C074636:amyloid beta-protein (25-35)
keywords: 5-month-old APP/PS1mice; Cognitive impairment; Neuritin; Synapse; miR-574