CpG preconditioning regulates miRNA expression that modulates genomic reprogramming associated with neuroprotection against ischemic injury

Vartanian, Keri B.; Mitchell, Hugh D.; Stevens, Susan; Conrad, Valerie K.; McDermott, Jason E.; Stenzel-Poore, Mary

doi:10.1038/jcbfm.2014.193

CpG preconditioning regulates miRNA expression that modulates genomic reprogramming associated with neuroprotection against ischemic injury

Journal Article · Sun Feb 01 04:00:00 EST 2015 · Journal of Cerebral Blood Flow and Metabolism

DOI:https://doi.org/10.1038/jcbfm.2014.193· OSTI ID:1710221

Vartanian, Keri B. ^[1]; Mitchell, Hugh D. ^[2]; Stevens, Susan ^[1]; Conrad, Valerie K. ^[1]; ^[2]; Stenzel-Poore, Mary ^[1]

Oregon Health & Science University
BATTELLE (PACIFIC NW LAB)

CpG preconditioning reprograms the genomic response to stroke to protect the brain against ischemic injury. The mechanisms that underlie genomic reprogramming are incompletely understood. MicroRNAs (miRNA) are novel regulators of gene expression; however, their potential role in modulating gene responses produced by CpG preconditioning is unknown. We evaluated brain miRNA expression in response to CpG preconditioning prior to and following stroke using microarray. Importantly, we have gene expression data from previous gene microarrays under the same conditions and timepoints, which allowed integration of miRNA and gene expression data to specifically identify regulated miRNA gene targets. Statistical analysis revealed that the miRNA targets were enriched in our regulated gene population, implicating that miRNAs likely orchestrate this gene expression. CpG and saline treatment shared expression of many miRNAs and their gene targets correlate with damaging upregulation of inflammation and protective suppression of metabolism and excitotoxicity. Excitingly, miRNAs that were differentially regulated between CpG and saline treated animals associated with the upregulation of several neuroprotective genes, indicating that these miRNAs are involved in genomic reprogramming to increase protection. This data suggests that miRNAs regulate endogenous responses to stroke and that manipulation of these miRNAs may have the potential to acutely activate novel protective responses to stroke.

Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE

DOE Contract Number:: AC05-76RL01830

OSTI ID:: 1710221

Report Number(s):: PNWD-SA-10412

Journal Information:: Journal of Cerebral Blood Flow and Metabolism, Journal Name: Journal of Cerebral Blood Flow and Metabolism Journal Issue: 2 Vol. 35

Country of Publication:: United States

Language:: English

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CpG preconditioning regulates miRNA expression that modulates genomic reprogramming associated with neuroprotection against ischemic injury

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