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The Dietary Excitotoxins β‐ N ‐Methylamino‐ l ‐Alanine and β‐ N ‐Oxalylamino‐ l ‐Alanine Induce Necrotic‐ and Apoptotic‐Like Death of Rat Cerebellar Granule Cells
Author(s) -
Staton Penelope C.,
Bristow David R.
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.69041508.x
Subject(s) - alanine , cerebellum , kynurenic acid , programmed cell death , glutamate receptor , biology , apoptosis , biochemistry , microbiology and biotechnology , granule (geology) , granule cell , amino acid , neuroscience , receptor , central nervous system , dentate gyrus , paleontology
The neurotoxic properties of the dietary excitotoxins β‐ N ‐methylamino‐ l ‐alanine and β‐ 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. β‐ N ‐Methylamino‐ l ‐alanine and β‐ N ‐oxalylamino‐ l ‐alanine, however, were toxic only after 24 or 48 h of exposure. The neurotoxic effects of β‐ N ‐methylamino‐ l ‐alanine were blocked by d (−)‐2‐amino‐5‐phosphonopentanoic acid, and those of β‐ 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 m M )‐ to a low K + (10 m M )‐containing medium. In cerebellar granule cells exposed to β‐ N ‐methylamino‐ l ‐alanine or β‐ N ‐oxalylamino‐ l ‐alanine (3 m M ), hallmarks of necrotic‐ and apoptotic‐like death were observed at various time points over a 72‐h period. Therefore, in cerebellar granule cells, β‐ N ‐methylamino‐ l ‐alanine and β‐ N ‐oxalylamino‐ l ‐alanine induce death over 12–72 h of exposure via a mechanism that involves both necrotic‐ and apoptotic‐like cell death.