Cytoprotective effect of NMDA receptor antagonists on prion protein (PrionSc)-induced toxicity in rat cortical cell cultures.
Rat cortical cells were incubated with the Scrapie prion protein, PrionSc. At concentrations of 3 ng/ml of PrionSc 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 PrionSc, PrionSc lost its deleterious effect on neurons. PrionSc did not affect the viability of astrocytes. Drugs known to block NMDA receptor channels, such as memantine (1-amino-3,5-dimethyl-adamantane) (Mem), its analogue 1-N-methylamino-3,5-dimethyl-adamantane as well as (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) prevented the effect of PrionSc. Production of PrionSc in the Scrapie prion-infected subclone of N2 a cells (ScN2 a cells) was not affected by memantine. We conclude that antagonists of the NMDA receptor-channel complex (i) abolish the PrionSc-induced neuronal injury in vitro, and (ii) display no influence on the synthesis and/or the processing of PrionSc.
Müller
W E
WE
Institut für Physiologische Chemie, Abteilung Angewandte Molekularbiologie, Universität, Mainz, Germany.
Ushijima
H
H
Schröder
H C
HC
Forrest
J M
JM
Schatton
W F
WF
Rytik
P G
PG
Heffner-Lauc
M
M
D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects*; D008081:Liposomes; D009419:Nerve Tissue Proteins / Q000633:toxicity*; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects; D018620:PrPSc Proteins; D011328:Prions / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured
D002121:Calcium Channel Blockers; D008081:Liposomes; D009419:Nerve Tissue Proteins; D018620:PrPSc Proteins; D011328:Prions; D016194:Receptors, N-Methyl-D-Aspartate