Beta-amyloid and oxidative stress jointly induce neuronal death, amyloid deposits, gliosis, and memory impairment in the rat brain.
Infusion of Fe2+, Abeta42, and buthionine-sulfoximine (FAB), but not Abeta42 alone or in combination with Fe2+, into the left cerebral ventricle of Long-Evans rats for 4 weeks induced memory impairment that was accompanied by increased hyperphosphorylated Tau protein levels in the CSF. FAB-infused animals displayed thioflavin-S-positive amyloid deposits, hyperphosphorylated Tau protein, neuronal loss, and gliosis. Animals treated with Abeta42, Fe2+, or buthionine-sulfoximine alone or in combination failed to show the histological modifications seen with FAB. This data suggests that Abeta42 is not sufficient to induce an Alzheimer's disease-like symptomatology, and it supports a model whereby a decrease in the brain's antioxidant defense system leads to the Abeta42-independent oxidative stress necessary for the peptide to induce histopathological changes and memory loss.
Lecanu
Laurent
L
Department of Biochemistry and Molecular Biology, Georgetown University Medical Center, Washington, DC 20057, USA.
Greeson
Janet
J
Papadopoulos
Vassilios
V
D000682:Amyloid / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D019328:Buthionine Sulfoximine / Q000008:administration & dosage / Q000494:pharmacology*; D016923:Cell Death; D002552:Cerebral Ventricles; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005296:Ferrous Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D005911:Gliosis / Q000139:chemically induced; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D020318:Rats, Long-Evans; D017382:Reactive Oxygen Species / Q000494:pharmacology
D000682:Amyloid; D016229:Amyloid beta-Peptides; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D005296:Ferrous Compounds; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C092862:amyloid beta-protein (10-43); C020748:ferrous sulfate; D019328:Buthionine Sulfoximine