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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Acute liver failure-induced hepatic encephalopathy is associated with changes in microRNA expression profiles in cerebral cortex of the rat

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Author(s):
Vemuganti, Raghu [1] ; Silva, Vinicius R. [2] ; Mehta, Suresh L. [1] ; Hazell, Alan S. [3, 2, 4]
Total Authors: 4
Affiliation:
[1] Univ Wisconsin, Dept Neurol Surg, Madison, WI - USA
[2] Univ Estadual Campinas UNICAMP, Dept Neurol, Campinas, SP - Brazil
[3] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7 - Canada
[4] CRCHUM, NeuroRescue Lab, Montreal, PQ H2X 0A9 - Canada
Total Affiliations: 4
Document type: Journal article
Source: METABOLIC BRAIN DISEASE; v. 29, n. 4, SI, p. 891-899, DEC 2014.
Web of Science Citations: 7
Abstract

The mechanisms that promote brain dysfunction after acute liver failure (ALF) are not clearly understood. The small noncoding RNAs known as microRNAs (miRNAs) significantly control mRNA translation and thus normal and pathological functions in the mammalian body. To understand their significance in ALF, we currently profiled the expression of miRNAs in the cerebral cortex of mice sacrificed at coma stage following treatment with azoxymethane. Of the 470 miRNAs profiled using microarrays, 37 were significantly altered (20 up-and 17 down-regulated) in their expression in the ALF group compared to sham group. In silico analysis showed that the ALF-responsive miRNAs target on average 231 mRNAs/miRNA (range: 3 to 840 targets). Pathways analysis showed that many miRNAs altered after ALF target multiple mRNAs that are part of various biological and molecular pathways. Glutamatergic synapse, Wnt signaling, MAP-kinase signaling, axon guidance, PI3-kinase-AKT signaling, T-cell receptor signaling and ubiquitin-mediated proteolysis are the top pathways targeted by the ALF-sensitive miRNAs. At least 28 ALF-responsive miRNAs target each of the above pathways. We hypothesize that alterations in miRNAs and their down-stream mRNAs of signaling pathways might play a role in the induction and progression of neurological dysfunction observed during ALF. (AU)

FAPESP's process: 11/02263-3 - Pathophysiology of cerebral glutamate transport dysfunction in acute liver failure
Grantee:Alan Stewart Hazell
Support type: Regular Research Grants
FAPESP's process: 12/15660-3 - Role of altered glutamatergic neurotransmission in acute liver failure (ALF).
Grantee:Vinícius Rodrigues Silva
Support type: Scholarships in Brazil - Doctorate