Overexpression of cellular prion protein alters postischemic
Erk1/2 phosphorylation but not Akt phosphorylation and protects against focal
cerebral ischemia
Affiliations: Department of Neurology, University of Jena Medical
School, 07747 Jena, Germany | Department of Neurology, University of Goettingen
Medical School, 37075 Goettingen, Germany | Department of Neuropathology, University of Goettingen
Medical School, 37075 Goettingen, Germany
Note: [] Corresponding author: Jens Weise, MD, Department of Neurology,
University of Jena Medical School, Erlanger Allee 101, 07747 Jena, Germany.
Tel.: +49 3641 9323413; Fax: +49 3641 9323412; E-mail:
[email protected]
Abstract: Purpose: The physiological function of the cellular prion protein
(PrP^{C}) is still unclear. A growing body of evidence suggests that
PrP^{C} has neuroprotective properties and that its deletion increases
susceptibility to focal cerebral ischemia. The purpose of this study was to
elucidate the role of PrP^{C} overexpression in ischemic brain injury in
vivo. Methods: PrP^{C} 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 PrP^{C}
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, PrP^{C} overexpression did not
change postischemic Akt phosphorylation, which acts anti-apoptotic and is
reduced in PrP^{C} knockout animals. Conclusions: These results
demonstrate that PrP^{C} 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 PrP^{C}
mediated neuroprotection.
