Changes in cortical and hippocampal ectonucleotidase activities in mice lacking cellular prion protein

Animals lacking cellular prion protein (PrPC) expression are more susceptib le to seizures. Adenosine is an endogenous anticonvulsant agent and it leve ls in the synaptic cleft are regulated by ectonucleotidases. We evaluated e ctonucleotidase activities in synaptosomes from hippocampus and cerebral co rtex of adult PrPC null mice and wild-type mice (genetic background 129/Sv X C57BL/6J). There was an increase (47%) in adenosine triphosphate (ATP) hy drolysis in hippocampal synaptosomes of PrPC knockout mice as compared with the wild-type animals. In cortical synaptosomes, ATP hydrolysis was simila r in both PrPC mice and controls. However, there was a significant decrease in adenosine diphosphate (ADP) hydrolysis in both hippocampal (-39%) and c ortical (-25%) synaptosomes in PrPC null animals compared to wild-type mice . Changes in brain ectonucleotidases activities related to modifications in the PrPC expression may contribute, at least in part, to the higher sensit ivity to seizures of PrPC null mice. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.