Cell death mechanisms in the early stages of acute glutamate neurotoxicity

The present study focused on the early stages of acute glutamate (L-Glu)-induced neurotoxic mechanisms, both biochemical, e.g intracellular reactive oxygen species (ROS) and associated parameters as well as gene expression of cell survival/death pathways, i.e Bcl-2 and caspases Stereotactic intracortical injections of L-Glu (1 mu mol/1 mu l) resulted in decreased size of pyramidal neurons in rat after 1 h We also observed that intracellular ROS, calcium (Ca(2+)) and peroxynitrite (ONOO(-)) production were significantly elevated, whereas, mitochondrial transmembrane potential (Delta Psi m) and total glutathione were significantly decreased by L-Glu bolus. The Bcl-2/Bax ratio in the I: Glu-injected rats was found to be significantly lower than the controls. Moreover, acute L-Glu significantly induced mRNA expression of nNOS, iNOS, caspase-3 and caspase-9 It may be concluded from the present Study that acute L-Glu administration, at an early stage. increases intracellular ROS accumulation, Ca(2+) levels and peroxynitrite production and decreases glutathione pool Furthermore, it appears that decreased mitochondrial Bcl-2/Bax ratio might have upregulated the mRNA expression of caspase-3 and caspase-9 which launch cell death cascade. Regarding the chronology of the events. we presume that acute L-GILT increases ROS and decreases Delta Psi m and glutathione rapidly and it is more likely that these events precede gene expression changes, ultimately resulting in neuronal damage/death (C) 2009 Elsevier Ireland Ltd anti the Japan Neuroscience Society All rights reserved