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NF-κB-regulated microRNA-574-5p underlies synaptic and cognitive impairment in response to atmospheric PM2.5 aspiration

Overview of attention for article published in Particle and Fibre Toxicology, August 2017
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Title
NF-κB-regulated microRNA-574-5p underlies synaptic and cognitive impairment in response to atmospheric PM2.5 aspiration
Published in
Particle and Fibre Toxicology, August 2017
DOI 10.1186/s12989-017-0215-3
Pubmed ID
Authors

Tingting Ku, Ben Li, Rui Gao, Yingying Zhang, Wei Yan, Xiaotong Ji, Guangke Li, Nan Sang

Abstract

PM2.5 (particulate matter ≤ 2.5 μm) is one of the leading environmental risk factors for the global burden of disease. Whereas increasing evidence has linked the adverse roles of PM2.5 with cardiovascular and respiratory diseases, limited but growing emerging evidence suggests that PM2.5 exposure can affect the nervous system, causing neuroinflammation, synaptic dysfunction and cognitive deterioration. However, the molecular mechanisms underlying the synaptic and cognitive deficits elicited by PM2.5 exposure are largely unknown. C57BL/6 mice received oropharyngeal aspiration of PM2.5 (1 and 5 mg/kg bw) every other day for 4 weeks. The mice were also stereotaxically injected with β-site amyloid precursor protein cleaving enzyme 1 (β-secretase, BACE1) shRNA or LV-miR-574-5p lentiviral constructs in the absence or presence of PM2.5 aspiration at 5 mg/kg bw every other day for 4 weeks. Spatial learning and memory were assessed with the Morris water maze test, and synaptic function integrity was evaluated with electrophysiological recordings of long-term potentiation (LTP) and immunoblot analyses of glutamate receptor subunit expression. The expression of α-secretase (ADAM10), BACE1, and γ-secretase (nicastrin) and the synthesis and accumulation of amyloid β (Aβ) were measured by immunoblot and enzyme-linked immunosorbent assay (ELISA). MicroRNA (miRNA) expression was screened with a microRNA microarray analysis and confirmed by real-time quantitative reverse transcription PCR (qRT-PCR) analysis. Dual-luciferase reporter gene and chromatin immunoprecipitation (ChIP) analyses were used to detect the binding of miR-574-5p in the 3'UTR of BACE1 and NF-κB p65 in the promoter of miR-574-5p, respectively. PM2.5 aspiration caused neuroinflammation and deteriorated synaptic function integrity and spatial learning and memory, and the effects were associated with the induction of BACE1. The action was mediated by NF-κB p65-regulated downregulation of miR-574-5p, which targets BACE1. Overexpression of miR-574-5p in the hippocampal region decreased BACE1 expression, restored synaptic function, and improved spatial memory and learning following PM2.5 exposure. Taken together, our findings reveal a novel molecular mechanism underlying impaired synaptic and cognitive function following exposure to PM2.5, suggesting that miR-574-5p is a potential intervention target for the prevention and treatment of PM2.5-induced neurological disorders.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 47 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 47 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 7 15%
Student > Bachelor 6 13%
Student > Master 5 11%
Student > Ph. D. Student 4 9%
Student > Doctoral Student 4 9%
Other 3 6%
Unknown 18 38%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 4 9%
Neuroscience 4 9%
Medicine and Dentistry 4 9%
Environmental Science 3 6%
Agricultural and Biological Sciences 3 6%
Other 7 15%
Unknown 22 47%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 April 2020.
All research outputs
#13,421,159
of 17,499,602 outputs
Outputs from Particle and Fibre Toxicology
#335
of 496 outputs
Outputs of similar age
#191,128
of 278,081 outputs
Outputs of similar age from Particle and Fibre Toxicology
#1
of 1 outputs
Altmetric has tracked 17,499,602 research outputs across all sources so far. This one is in the 20th percentile – i.e., 20% of other outputs scored the same or lower than it.
So far Altmetric has tracked 496 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.8. This one is in the 27th percentile – i.e., 27% of its peers scored the same or lower than it.
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