High levels of Cellular Prion Protein improve astrocyte development

Prion protein (PrPC) has neuroprotective functions and herein we demonstrate that astrocytes from PrPC-over-expressing mice are more resistant to induced cell death than wild-type astrocytes. The Stress-Inducible-Protein 1 (STI1), a PrPC ligand, prevents cell death in both wild-type and PrPC-over-expressing astrocytes through the activation of protein-kinase-A. Cultured embryonic astrocytes and brain extracts from PrPC-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 PrPC levels modulate astrocyte development, and that PrPC–STI1 interaction contributes to protect against astrocyte death.

► PrPC over-expression promotes resistance to death and early maturation of astrocytes. ► PrPC interacts with STI1 and induces astrocyte survival through the PKA pathway. ► ERK1/2 activity is increased in PrPC over-expressing astrocytes. ► PrPC levels regulate GFAP, vimentin and nestin expression during brain development.