High levels of cellular prion protein improve astrocyte development

Prion protein (PrP(C)) has neuroprotective functions and herein we demonstrate that astrocytes from PrP(C)-over-expressing mice are more resistant to induced cell death than wild-type astrocytes. The Stress-Inducible-Protein 1 (STI1), a PrP(C) ligand, prevents cell death in both wild-type and PrP(C)-over-expressing astrocytes through the activation of protein-kinase-A. Cultured embryonic astrocytes and brain extracts from PrP(C)-over-expressing mice show higher glial fibrillary acidic protein expression and reduced vimentin and nestin levels when compared to wild-type astrocytes, suggesting faster astrocyte maturation in the former mice. Our data indicate that PrP(C) levels modulate astrocyte development, and that PrP(C)-STI1 interaction contributes to protect against astrocyte death.