期刊
SCIENTIFIC REPORTS
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/srep34433
关键词
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资金
- Korea Healthcare Technology R&D Project by Ministry for Health, Welfare and Family Affairs, Republic of Korea [HI11C1186, HI12C0983]
- National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [20110021866]
- Seoul National University Bundang Hospital Research Fund [03-2012-016]
- BK21-plus education program by the National Research Foundation of Korea
- UK Wellcome Trust-MRC Neurodegenerative Disease Initiative Programme
- Wolfson Research Merit Award, the Royal Society London
- Biotechnology and Biological Sciences Research Council [BB/N001893/1] Funding Source: researchfish
- BBSRC [BB/N001893/1, BB/G003963/1] Funding Source: UKRI
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 A beta(1-42) treatment diminished miR-188-5p expression in primary hippocampal neuron cultures and that miR-188-5p rescued the A beta(1-42)-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 A beta(1-42) and 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 A beta-mediated pathophysiology in the disease.
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