title: Upregulation of cellular prion protein (PrPc) after focal cerebral ischemia and influence of lesion severity.
abstract: The pathological isoform of the prion protein (PrP(Sc)) has been identified to mediate transmissible spongiform encephalopathies like Creutzfeldt-Jakob disease (CJD). In contrast, the physiological function of the normal cellular prion protein (PrP(c)) is not yet understood. Recent findings suggest that PrP(c) may have neuroprotective properties and that its absence increases susceptibility to oxidative stress and neuronal injury. To determine whether PrP(c) is part of the cellular response to neuronal injury in vivo, we investigated PrP(c) regulation after severe and mild focal ischemic brain injury in mice using the thread occlusion stroke model. Western Blot and ELISA analysis showed a significant upregulation of PrP(c) in the ischemic hemisphere at 4 and 8h after onset of permanent focal ischemia, which was no longer detectable at 24h after lesion induction when compared to control animals. In contrast, transient focal ischemia (60 min) did only lead to slightly but not significantly elevated PrP(c) levels in the ischemic hemisphere when compared to controls. These results demonstrate that cerebral PrP(c) is upregulated early in response to focal cerebral ischemia. The extent of upregulation, however, seems to depend on the severity of ischemia and may therefore reflect the extent of ischemia induced neuronal damage. Given the known neuroprotective effects of PrP(c) in vitro, ischemia-induced upregulation of cerebral PrP(c) supports the hypothesis that, as part of an early adaptive cellular response to ischemic brain injury, PrP(c) may be involved in the regulation of ischemia-induced neuronal cell death in vivo.
authors.affiliation: Department of Neurology, University of Goettingen Medical School, Robert-Koch-Str. 40, 37075 Goettingen, Germany. jweise@gwdg.de
authors.forename: Jens
authors.initials: J
authors.lastname: Weise
authors.forename: Olaf
authors.initials: O
authors.lastname: Crome
authors.forename: Raoul
authors.initials: R
authors.lastname: Sandau
authors.forename: Walter
authors.initials: W
authors.lastname: Schulz-Schaeffer
authors.forename: Mathias
authors.initials: M
authors.lastname: Bähr
authors.forename: Inga
authors.initials: I
authors.lastname: Zerr
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018621:PrPC Proteins / Q000096:biosynthesis*; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D018621:PrPC Proteins