title: MicroRNA-139 modulates Alzheimer's-associated pathogenesis in SAMP8 mice by targeting cannabinoid receptor type 2.
abstract: Alzheimer's disease (AD) is a neurodegenerative disorder, and is the most common type of dementia in the elderly population. Growing evidence indicates that microRNAs (miRNAs) play a crucial role in neuroinflammation associated with AD progression. In this study, we analyzed the expression of microRNA-139 (miR-139) as well as the learning and memory function in AD. We observed that the miR-139 expression was significantly higher in the hippocampus of aged senescence accelerated mouse prone 8 (SAMP8) mice (2.92 ± 0.13) than in the control mice (1.49 ± 0.08). Likewise, the overexpression of miR-139 by means of hippocampal injection impaired the hippocampus-dependent learning and memory formation. In contrast, the downregulation of miR-139 in mice improved learning and memory function in the mice. The level of cannabinoid receptor type 2 (CB2), a potential target gene of miR-139, was inversely correlated with the miR-139 expression in primary hippocampal cells. Furthermore, we demonstrated that miR-139 inversely modulated the responses to proinflammatory stimuli. Together, our findings demonstrate that miR-139 exerts a pathogenic effect in AD by modulating CB2-meditated neuroinflammatory processes.
authors.affiliation: Department of Geriatric, Wuxi No. 2 People's Hospital, Wuxi, Jiangsu, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Geriatric, Wuxi No. 2 People's Hospital, Wuxi, Jiangsu, China.
authors.forename: J S
authors.initials: JS
authors.lastname: Bao
authors.affiliation: Department of Geriatric, Wuxi No. 2 People's Hospital, Wuxi, Jiangsu, China.
authors.forename: J H
authors.initials: JH
authors.lastname: Su
authors.affiliation: Department of Geriatric, Wuxi No. 2 People's Hospital, Wuxi, Jiangsu, China jiaxiya2000@163.com.
authors.forename: W
authors.initials: W
authors.lastname: Huang
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000523:psychology*; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018782:Maze Learning; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics* / Q000378:metabolism
chemical_list: D016207:Cytokines; C546202:MIRN139 microRNA, mouse; D035683:MicroRNAs; D043885:Receptor, Cannabinoid, CB2