The dietary excitotoxins beta-N-methylamino-L-alanine and beta-N-oxalylamino-L-alanine induce necrotic- and apoptotic-like death of rat cerebellar granule cells.

Abstract:

:The neurotoxic properties of the dietary excitotoxins beta-N-methylamino-L-alanine and beta-N-oxalylamino-L-alanine have been studied in rat cerebellar granule cells and compared with those of glutamate. Glutamate caused dose-dependent death of cerebellar granule cells after a 30-min exposure when viability was assessed 24 h later. Beta-N-methylamino-L-alanine and beta-N-oxalylamino-L-alanine, however, were toxic only after 24 or 48 h of exposure. The neurotoxic effects of beta-N-methylamino-L-alanine were blocked by D(-)-2-amino-5-phosphonopentanoic acid, and those of beta-N-oxalylamino-L-alanine were blocked by kynurenic acid, which demonstrated that these excitotoxins caused cerebellar granule cell death through the activation of glutamate receptors. The features of this death were examined morphologically (fluorescent dyes, electron microscopy) and biochemically (conventional agarose gel electrophoresis, effect of aurintricarboxylic acid). Characteristics of apoptosis were identified by transferring cerebellar granule cells from a high K+ (30 mM)- to a low K+ (10 mM)-containing medium. In cerebellar granule cells exposed to beta-N-methylamino-L-alanine or beta-N-oxalylamino-L-alanine (3 mM), hallmarks of necrotic- and apoptotic-like death were observed at various time points over a 72-h period. Therefore, in cerebellar granule cells, beta-N-methylamino-L-alanine and beta-N-oxalylamino-L-alanine induce death over 12-72 h of exposure via a mechanism that involves both necrotic- and apoptotic-like cell death.

journal_name

J Neurochem

authors

Staton PC,Bristow DR

doi

10.1046/j.1471-4159.1997.69041508.x

subject

Has Abstract

pub_date

1997-10-01 00:00:00

pages

1508-18

issue

4

eissn

0022-3042

issn

1471-4159

journal_volume

69

pub_type

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