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Alterations in serum microRNA in humans with alcohol use disorders impact cell proliferation and cell death pathways and predict structural and functional changes in brain

Overview of attention for article published in BMC Neuroscience, September 2015
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Title
Alterations in serum microRNA in humans with alcohol use disorders impact cell proliferation and cell death pathways and predict structural and functional changes in brain
Published in
BMC Neuroscience, September 2015
DOI 10.1186/s12868-015-0195-x
Pubmed ID
Authors

Cherry Ignacio, Steven D. Hicks, Patrick Burke, Lambert Lewis, Zsuzsa Szombathyne-Meszaros, Frank A. Middleton

Abstract

There is currently a lack of reliable, minimally invasive biomarkers that could predict the extent of alcoholism-induced CNS damage. Developing such biomarkers may prove useful in reducing the prevalence of alcohol use disorders (AUDs). Extracellular microRNAs (miRNAs) can be informative molecular indicators of changes in neuronal gene expression. In this study, we performed a global analysis of extracellular miRNAs to identify robust biomarkers of early CNS damage in humans diagnosed with DSM-IV AUDs. We recruited a relatively young set of 20 AUD subjects and 10 age-matched controls. They were subjected to comprehensive medical, neuropsychological and neuroimaging tests, followed by comparison of miRNA levels found in peripheral blood serum. Employing a conservative strategy to identify candidate biomarkers, miRNAs were quantified using two independent high-throughput methods: microarray and next-generation RNA-sequencing. This improved our capacity to discover and validate relevant miRNAs. Our results identified several miRNAs with significant and reproducible expression changes in AUD subjects versus controls. Moreover, several significant associations between candidate miRNA biomarkers and various medical, neuropsychological and neuroimaging parameters were identified using Pearson correlation and unbiased hierarchical clustering analyses. Some of the top candidate biomarkers identified, such as mir-92b and mir-96 have established roles in neural development. Cross-species validation of miRNA expression was performed using two different in vivo rat drinking models and two different in vitro mouse neural stem cell exposure models. A systems level analysis revealed a remarkable degree of convergence in the top changes seen in all of these data sets, specifically identifying cell death, cell proliferation and cell cycle processes as most consistently affected. Though not necessarily the same molecules, the affected miRNAs within these pathways clearly influence common genes, such as p53 and TNF, which stand out as potential keystone molecules. Lastly, we also examined the potential tissue origins of these biomarkers by quantifying their levels in 15 different tissue types and show that several are highly-enriched in the brain. Collectively, our results suggest that serum miRNA expression changes can directly relate to alterations in CNS structure and function, and may do so through effects on highly specific cellular pathways.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 82 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 1%
Czechia 1 1%
Unknown 80 98%

Demographic breakdown

Readers by professional status Count As %
Researcher 15 18%
Student > Master 10 12%
Student > Bachelor 9 11%
Student > Ph. D. Student 7 9%
Student > Doctoral Student 5 6%
Other 14 17%
Unknown 22 27%
Readers by discipline Count As %
Medicine and Dentistry 14 17%
Agricultural and Biological Sciences 11 13%
Biochemistry, Genetics and Molecular Biology 9 11%
Neuroscience 7 9%
Pharmacology, Toxicology and Pharmaceutical Science 3 4%
Other 14 17%
Unknown 24 29%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 07 September 2015.
All research outputs
#13,955,130
of 22,826,360 outputs
Outputs from BMC Neuroscience
#584
of 1,244 outputs
Outputs of similar age
#133,420
of 267,371 outputs
Outputs of similar age from BMC Neuroscience
#10
of 22 outputs
Altmetric has tracked 22,826,360 research outputs across all sources so far. This one is in the 37th percentile – i.e., 37% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,244 research outputs from this source. They receive a mean Attention Score of 4.3. This one has gotten more attention than average, scoring higher than 51% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 267,371 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 48th percentile – i.e., 48% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 22 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 50% of its contemporaries.