Replenishment of microRNA-188-5p restores the synaptic and cognitive deficits in 5XFAD Mouse Model of Alzheimer’s Disease.
SCIE
SCOPUS
- Title
- Replenishment of microRNA-188-5p restores the synaptic and cognitive deficits in 5XFAD Mouse Model of Alzheimer’s Disease.
- Authors
- Lee, K; Kim, H; An, K; Kwon, OB; Park, S; Cha, JH; Kim, MH; Lee, Y; Kim, JH; Cho, K; Kim, HS
- Date Issued
- 2016-10-06
- Publisher
- Nature Publishing Group
- 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 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.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/37105
- DOI
- 10.1038/SREP34433
- ISSN
- 2045-2322
- Article Type
- Article
- Citation
- Scientific Reports, vol. 6, 2016-10-06
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