Age-associated oxidative stress has been implicated in neuronal damage linked with Alzheimer's disease (AD). In addition to the role of beta-amyloid peptide (A beta) in the pathogenesis of AD, reduced glucose oxidative metabolism and decreased mitochondrial activity have been suggested as associated factors. However, the relationship between A toxicity, metabolic impairment, and oxidative stress is far from being understood. In vivo neurotoxicity of A beta 25-35 peptide has been conflicting. However, in previous studies, we have shown that A beta 25-35 consistently induces synaptic toxicity and neuronal death in the hippocampus in vivo, when administered during moderate glycolytic or mitochondrial inhibition. In the present study, we have investigated whether enhancement of A beta neurotoxicity during these conditions involves oxidative stress. Results show increased lipoperoxidation (LPO) when A is administered in the hippocampus of rats previously treated with the glycolysis inhibitor, iodoacetate. Neuronal damage and LPO are efficiently prevented by vitamin E, while the spin trapper, alpha-phenyl-N-tert-butyl nitrone, shows partial protection. A beta stimulates LPO in synaptosomes, but toxicity is only observed in the presence of metabolic inhibitors. Damage and LPO are efficiently prevented by vitamin E. The present results suggest an interaction between oxidative stress and metabolic impairment in the A beta neurotoxic cascade. (c) 2006 Elsevier Inc. All rights reserved.
Última actualización: 14/11/2018