CYTOPROTECTIVE EFFECT OF NMDA RECEPTOR ANTAGONISTS ON PRION PROTEIN (PRION(SC))-INDUCED TOXICITY IN RAT CORTICAL CELL-CULTURES

Rat cortical cells were incubated with the Scrapie prion protein, Prion(Sc). At concentrations of 3 ng/ml of Prion(Sc) and higher, the viability of the cells decreased significantly after a 12-h incubation period. Simultaneously, the degree of DNA fragmentation increased. In control experiments with antibodies against Prion(Sc), Prions' lost its deleterious effect on neurons. Prion(Sc) did not affect the viability of astrocytes. Drugs known to block NMDA receptor channels, such as memantine (1-amino-3,5-dimethyladamantane) (Mem), its analogue 1-N-methylamino-3,5-dimethyl-adamantane as well as (+)-5-methyl-10,11-dihydro-5H-di-benzo[a,d]cyclohepten-5,10-imine maleate (MK-801) prevented the effect of Prion(Sc). Production of Prion(Sc) in the Scrapie prion-infected subclone of N2a cells (ScN2a cells) was not affected by memantine. We conclude that antagonists of the NMDA receptor-channel complex (i) abolish the Prion(Sc)-induced neuronal injury in vitro, and (ii) display no influence on the synthesis and/or the processing of Prion(Sc).