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.
