title: Overexpression of cellular prion protein alters postischemic Erk1/2 phosphorylation but not Akt phosphorylation and protects against focal cerebral ischemia.
abstract: OBJECTIVE
  The physiological function of the cellular prion protein (PrPC) is still unclear. A growing body of evidence suggests that PrPC has neuroprotective properties and that its deletion increases susceptibility to focal cerebral ischemia. The purpose of this study was to elucidate the role of PrPC overexpression in ischemic brain injury in vivo.
  
  
  METHODS
  PrPC overexpressing (TG35) and wild type (WT) mice were subjected to a 90-minute transient focal cerebral ischemia followed by infarct volume analysis 24 hours after lesion. To identify effects of PrPC overexpression on signalling pathways important for the regulation of ischemic cell death, we studied postischemic activation and expression of Akt and Erk1/2 using quantitative Western Blot analysis.
  
  
  RESULTS
  TG35 mice displayed significantly smaller infarct volumes and showed reduced early postischemic Erk1/2 phosphorylation, a pathway known to exacerbate neuronal injury following transient cerebral ischemia. In contrast, PrPC overexpression did not change postischemic Akt phosphorylation, which acts anti-apoptotic and is reduced in PrPC knockout animals.
  
  
  CONCLUSIONS
  These results demonstrate that PrPC overexpression reduces deleterious Erk1/2 activation but does not affect Akt activation after transient cerebral ischemia, suggesting a role for distinct cytosolic signalling pathways in PrPC mediated neuroprotection.
authors.affiliation: Department of Neurology, University of Jena Medical School, 07747 Jena, Germany. jens.weise@med.uni-jena.de
authors.forename: Jens
authors.initials: J
authors.lastname: Weise
authors.forename: Thorsten R
authors.initials: TR
authors.lastname: Doeppner
authors.forename: Tilo
authors.initials: T
authors.lastname: Müller
authors.forename: Arne
authors.initials: A
authors.lastname: Wrede
authors.forename: Walter
authors.initials: W
authors.lastname: Schulz-Schaeffer
authors.forename: Inga
authors.initials: I
authors.lastname: Zerr
authors.forename: Otto W
authors.initials: OW
authors.lastname: Witte
authors.forename: Mathias
authors.initials: M
authors.lastname: Bähr
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000517:prevention & control*; D002544:Cerebral Infarction / Q000209:etiology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism* / Q000502:physiology; D008954:Models, Biological; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D010766:Phosphorylation; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
chemical_list: D018621:PrPC Proteins; D051058:Oncogene Protein v-akt; D048052:Mitogen-Activated Protein Kinase 3