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

doi:10.1016/0922-4106(93)90040-G

European Journal of Pharmacology: Molecular Pharmacology

Volume 246, Issue 3, 15 August 1993, Pages 261-267

https://doi.org/10.1016/0922-4106(93)90040-G Get rights and content

Abstract

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, 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 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 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/or the processing of Prion^Sc.

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Research paperCytoprotective effect of NMDA receptor antagonists on prion protein (PrionSc)-induced toxicity in rat cortical cell cultures

Abstract

J. Biol. Chem.

Eur. J. Pharmacol.

Eur. J. Pharmacol.

J. Biol. Chem.

Exp. Cell. Res.

Arch. Biochem. Biophys.

Eur. J. Pharmacol.

Eur. J. Pharmacol.

Trends Neurosci.

Eur. J. Pharmacol (Mol. Pharmacol. Sec.)

Eur. J. Pharmacol.

Cell

Neural cell adhesion molecules modulate tyrosine phosphorylation of tubulin in nerve growth cone membranes

Neuron

Apoptosis: mode of cell death induced in T cell leukemia lines by dexamethasone and other agents

FASEB J.

Growth and cultivation of dissociated neurons and glial cells from embryonic chick, rat and human brain in flask cultures

Neurobiology

Identification of a protein that purifies with the scrapie prion

Science

Biological evidence that scrapie agent has an independent genome

J. Gen. Virol.

Study of the condition and mechanism of diphenylamine reactions for the colorimetric estimation of deoxyribonucleic acid

Biochem. J.

Scrapie-infected murine neuroblastoma cells produce protease-resistant prion proteins

J. Virol.

Prion protein biosynthesis in scrapie-infected and uninfected neuroblastoma cells

J. Virol.

Monoclonal antibodies specific for glial fibrillary acidic (GFA) protein and for each of the neurofilament triplet polypeptides

Differentiation

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