title: MicroRNAs participate in the murine oligodendroglial response to perinatal hypoxia-ischemia.
abstract: BACKGROUND
  Hypoxic-ischemic injury (HI) to preterm brain results in white matter loss. The endogenous oligodendroglial response to perinatal HI is characterized by increased oligodendroglial progenitor cells (OPCs). MicroRNAs (miRs) are important post-transcriptional regulators of gene expression, and a few miRs have been shown to regulate differentiation of OPCs into mature oligodendroglia. We tested the hypothesis that miRs play a role in the increase in OPCs in response to perinatal HI.
  
  
  METHODS
  We inducibly deleted the miR-processing enzyme Dicer in OPCs using a tamoxifen-inducible NG2CreER(T2) transgene in Dicer(fl/fl) mice. After HI, mice were analyzed for OPC differentiation using immunofluorescence and for white matter formation by Luxol fast blue (LFB) staining. Functional recovery from injury was investigated using digital gait analysis. We also tested whether HI changed miRs known to regulate OPC differentiation using quantitative RT-PCR.
  
  
  RESULTS
  Perinatal HI induced significant increases in miR-138 and miR-338, two miRs known to regulate OPC differentiation. Knockdown of Dicer increased myelin basic protein and LFB staining within the corpus callosum after HI. In addition, there was significant improvement in motor function 14 and 24 d post lesion.
  
  
  CONCLUSIONS
  Changes in specific mature miRs expressed in OPCs following HI may contribute to white matter injury.
authors.affiliation: Department of Neurology, Northwestern University, Chicago, Illinois.
authors.forename: Derin
authors.initials: D
authors.lastname: Birch
authors.affiliation: Department of Neurology, Northwestern University, Chicago, Illinois.
authors.forename: Blair C
authors.initials: BC
authors.lastname: Britt
authors.affiliation: Department of Pediatrics, Northwestern University, Chicago, Illinois.
authors.forename: Silena C
authors.initials: SC
authors.lastname: Dukes
authors.affiliation: Department of Neurology, Northwestern University, Chicago, Illinois.
authors.forename: John A
authors.initials: JA
authors.lastname: Kessler
authors.affiliation: Department of Pediatrics, Northwestern University, Chicago, Illinois.
authors.forename: Maria L V
authors.initials: ML
authors.lastname: Dizon
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000502:physiology; D053487:DEAD-box RNA Helicases / Q000235:genetics; D055785:Gene Knockdown Techniques; D020925:Hypoxia-Ischemia, Brain / Q000235:genetics* / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000502:physiology*; D009836:Oligodendroglia / Q000502:physiology*; D043244:Ribonuclease III / Q000235:genetics
chemical_list: D035683:MicroRNAs; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases