title: Role of oxidative stress on beta-amyloid neurotoxicity elicited during impairment of energy metabolism in the hippocampus: protection by antioxidants.
abstract: 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 (Abeta) in the pathogenesis of AD, reduced glucose oxidative metabolism and decreased mitochondrial activity have been suggested as associated factors. However, the relationship between Abeta toxicity, metabolic impairment, and oxidative stress is far from being understood. In vivo neurotoxicity of Abeta25-35 peptide has been conflicting. However, in previous studies, we have shown that Abeta25-35 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 Abeta neurotoxicity during these conditions involves oxidative stress. Results show increased lipoperoxidation (LPO) when Abeta 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. Abeta 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 Abeta neurotoxic cascade.
authors.affiliation: Departamento de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México AP 70-253, México DF 04510, México.
authors.forename: Teresa
authors.initials: T
authors.lastname: Montiel
authors.forename: Ricardo
authors.initials: R
authors.lastname: Quiroz-Baez
authors.forename: Lourdes
authors.initials: L
authors.lastname: Massieu
authors.forename: Clorinda
authors.initials: C
authors.lastname: Arias
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D004195:Disease Models, Animal; D004347:Drug Interactions; D004734:Energy Metabolism / Q000187:drug effects*; D005986:Glyceraldehyde 3-Phosphate / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D013385:Succinate Dehydrogenase / Q000378:metabolism; D014810:Vitamin E / Q000008:administration & dosage
chemical_list: D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D014810:Vitamin E; D005986:Glyceraldehyde 3-Phosphate; D000255:Adenosine Triphosphate; D013385:Succinate Dehydrogenase