title: Ischemic preconditioning regulates expression of microRNAs and a predicted target, MeCP2, in mouse cortex.
abstract: Preconditioning describes the ischemic stimulus that triggers an endogenous, neuroprotective response that protects the brain during a subsequent severe ischemic injury, a phenomenon known as 'tolerance'. Ischemic tolerance requires new protein synthesis, leads to genomic reprogramming of the brain's response to subsequent ischemia, and is transient. MicroRNAs (miRNAs) regulate posttranscriptional gene expression by exerting direct effects on messenger RNA (mRNA) translation. We examined miRNA expression in mouse cortex in response to preconditioning, ischemic injury, and tolerance. The results of our microarray analysis revealed that miRNA expression is consistently altered within each group, but that preconditioning was the foremost regulator of miRNAs. Our bioinformatic analysis results predicted that preconditioning-regulated miRNAs most prominently target mRNAs that encode transcriptional regulators; methyl-CpG binding protein 2 (MeCP2) was the most prominent target. No studies have linked MeCP2 to preconditioning or tolerance, yet miR-132, which regulates MeCP2 expression, is decreased in preconditioned cortex. Downregulation of miR-132 is consistent with our finding that preconditioning ischemia induces a rapid increase in MeCP2 protein, but not mRNA, in mouse cortex. These studies reveal that ischemic preconditioning regulates expression of miRNAs and their predicted targets in mouse brain cortex, and further suggest that miRNAs and MeCP2 could serve as effectors of ischemic preconditioning-induced tolerance.
authors.affiliation: Robert S. Dow Neurobiology Laboratories, Legacy Research, Portland, Oregon 97232, USA.
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Lusardi
authors.forename: Carol D
authors.initials: CD
authors.lastname: Farr
authors.forename: Craig L
authors.initials: CL
authors.lastname: Faulkner
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pignataro
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.forename: Jingquan
authors.initials: J
authors.lastname: Lan
authors.forename: Roger P
authors.initials: RP
authors.lastname: Simon
authors.forename: Julie A
authors.initials: JA
authors.lastname: Saugstad
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism; D002540:Cerebral Cortex / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D019194:Ischemic Preconditioning; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D046228:Microarray Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C546976:MIRN132 microRNA, mouse; D051783:Methyl-CpG-Binding Protein 2; D035683:MicroRNAs; D012333:RNA, Messenger