Naslov
Cytoprotective effect of NMDA receptor antagonists on prion protein (Prion Sc)-induced toxicity in rat cortical cell cultures

Autori
Muller, Werner E G ; Ushijima, Hiroshi ; Schroder, Heinz C ; Forrest, Jock M S ; Schatton, Wolfgang F H ; Rytik, Peter G ; Heffer-Lauc, Marija

Izvornik
European journal of pharmacology. Molecular pharmacology section (0922-4106) 246 (1993), 3; 261-267

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Scrapie; cortical cells; mamantine; NMDA receptor; neurons; prion; adamantanes; MK-801
(NMDA receptor; neurons; prion; adamantanes; MK-801)

Sažetak
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 agonists Prion sc, Prion sc lost its deleterious effect on neurons. Prion sc did not affect the viability of astrocytes. Drugs known to block NMDA receptor channels, such as mamantine (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 Prion sc. Production of Prion sc in the Scrapie prion-infected subclone of N_2a cells (ScN_2a cells) was not affected by memantine. We conclude that antagonists of the NMDA receptor-chnnel 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.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA