title: Ischemic pre-conditioning alters cerebral microRNAs that are upstream to neuroprotective signaling pathways.
abstract: Cerebral gene expression is known to be significantly influenced by a sublethal ischemic event (pre-conditioning; PC) that induces tolerance to future damaging ischemic events. Small non-coding RNAs known as microRNAs (miRNAs) were recently shown to control the mRNA translation. We currently profiled cerebral miRNAs in the cerebral cortex of rats subjected to PC. The miRNAome reacted quickly and by 6 h following PC, levels of 51 miRNAs were altered (26 up- and 25 down-regulated; > 1.5-fold change). Twenty of these stayed at the altered level even at 3 days after PC. At least nine miRNAs showed > 5-fold change at one or more time points between 6 h to 3 days after PC compared with sham. Bioinformatics analysis showed 2007 common targets of the miRNAs that were up-regulated and 459 common targets of the miRNAs that were down-regulated after PC. Pathways analysis showed that MAP-kinase and Mammalian target of rapamycin (mTOR) signaling are the top two Kyoto Encyclopedia of Genes and Genomes pathways targeted by the up-regulated miRNAs, and Wnt and GnRH signaling are the top two Kyoto Encyclopedia of Genes and Genomes pathways targeted by the down-regulated miRNAs after PC. We hypothesize that alterations in miRNAs and their down-stream mRNAs of signaling pathways might play a role in the induction of ischemic tolerance.
authors.affiliation: Department of Neurological Surgery and Neuroscience Training Program, University of Wisconsin, Madison, Wisconsin 53792, USA.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Dharap
authors.forename: Raghu
authors.initials: R
authors.lastname: Vemuganti
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D019295:Computational Biology; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000502:physiology*; D053263:Gene Regulatory Networks / Q000502:physiology*; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D051381:Rats; D011918:Rats, Inbred SHR; D015398:Signal Transduction / Q000502:physiology*; D013997:Time Factors
chemical_list: D035683:MicroRNAs
references.citation: Genes Dev. 2004 Dec 1;18(23):2893-904
references.pmid: 15545625
references.citation: Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):436-41
references.pmid: 10618436
references.citation: J Biol Chem. 2003 Aug 8;278(32):29655-60
references.pmid: 12777372
references.citation: Lancet Neurol. 2009 Nov;8(11):1056-72
references.pmid: 19833297
references.citation: Stroke. 1998 Sep;29(9):1937-50; discussion 1950-1
references.pmid: 9731622
references.citation: J Biol Chem. 2002 Oct 18;277(42):39728-38
references.pmid: 12145288
references.citation: Neurobiol Dis. 2006 Jan;21(1):18-28
references.pmid: 16040250
references.citation: Mol Cells. 2009 Dec 31;28(6):501-7
references.pmid: 20047076
references.citation: J Cell Sci. 2006 Jan 1;119(Pt 1):162-71
references.pmid: 16371654
references.citation: Bioinformatics. 2009 Aug 1;25(15):1991-3
references.pmid: 19435746
references.citation: J Cereb Blood Flow Metab. 2008 Jun;28(6):1104-13
references.pmid: 18319730
references.citation: J Cell Biol. 2001 Jan 8;152(1):87-96
references.pmid: 11149923
references.citation: Neurobiol Dis. 2010 Apr;38(1):17-26
references.pmid: 20053374
references.citation: Neurochem Int. 2006 Jul;49(2):127-35
references.pmid: 16759752
references.citation: Genome Res. 2009 Jan;19(1):92-105
references.pmid: 18955434
references.citation: PLoS Biol. 2004 Nov;2(11):e363
references.pmid: 15502875
references.citation: J Cereb Blood Flow Metab. 2009 Apr;29(4):675-87
references.pmid: 19142192
references.citation: Nucleic Acids Res. 2008 Jan;36(Database issue):D149-53
references.pmid: 18158296
references.citation: Science. 2002 Dec 6;298(5600):1911-2
references.pmid: 12471242
references.citation: Brain Res Mol Brain Res. 2002 Jun 30;103(1-2):106-15
references.pmid: 12106696
references.citation: Eur J Cardiothorac Surg. 1997 Aug;12(2):261-7
references.pmid: 9288517
references.citation: J Neurosci. 2002 Jul 15;22(14):5879-88
references.pmid: 12122050
references.citation: Stroke. 2007 Feb;38(2 Suppl):680-5
references.pmid: 17261715
references.citation: J Cereb Blood Flow Metab. 2010 Jan;30(1):92-101
references.pmid: 19724284
references.citation: Histol Histopathol. 2006 Jan;21(1):103-24
references.pmid: 16267791
references.citation: FASEB J. 2009 Jun;23(6):1625-37
references.pmid: 19141537
references.citation: J Neurochem. 2004 Apr;89(1):73-89
references.pmid: 15030391
references.citation: Science. 2006 Jul 21;313(5785):320-4
references.pmid: 16809489
references.citation: Cell. 2009 Jan 23;136(2):215-33
references.pmid: 19167326
references.citation: Cardiovasc Res. 2002 Aug 15;55(3):602-18
references.pmid: 12160958
references.citation: Lancet Neurol. 2009 Apr;8(4):398-412
references.pmid: 19296922
references.citation: Brain Res. 2007 Oct 26;1177:103-23
references.pmid: 17916339
references.citation: Cell. 2005 Jan 14;120(1):15-20
references.pmid: 15652477
references.citation: Stroke. 2008 Mar;39(3):959-66
references.pmid: 18258830
references.citation: Cancer Sci. 2010 Mar;101(3):700-6
references.pmid: 20085589
references.citation: Neurobiol Dis. 2009 Aug;35(2):264-9
references.pmid: 19465127
references.citation: Brain Res. 2004 Nov 19;1027(1-2):30-7
references.pmid: 15494154
references.citation: Bioinformatics. 2003 Jan 22;19(2):185-93
references.pmid: 12538238
references.citation: J Neurochem. 2009 Apr;109(1):287-94
references.pmid: 19200341