Protective effects of idebenone and α-tocopherol on β-amyloid-(1-42)-induced learning and memory deficits in rats: implication of oxidative stress in β-amyloid-induced neurotoxicity in vivo

• Published in: The European journal of neuroscience 1999-01, Vol.11 (1), p.83-90
• Main Authors: Yamada, Kiyofumi, Tanaka, Tomoko, Han, Daiken, Senzaki, Kouji, Kameyama, Tsutomu, Nabeshima, Toshitaka
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid beta-Peptides - pharmacology; Animals; Antioxidants - pharmacology; Avoidance Learning - drug effects; Benzoquinones - pharmacology; Brain Chemistry - drug effects; Drug Interactions; Injections, Intraventricular; lipid peroxidation; Lipid Peroxidation - drug effects; Locomotion - drug effects; Male; Maze Learning - drug effects; Memory - drug effects; Nerve Degeneration - chemically induced; Nerve Degeneration - physiopathology; Neurotoxins - pharmacology; Oxidative Stress - physiology; Peptide Fragments - pharmacology; Rats; Rats, Wistar; reference memory; Ubiquinone - analogs & derivatives; Vitamin E - pharmacology; working memory
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1046/j.1460-9568.1999.00408.x

Amyloid β‐peptide (Aβ), the major constituent of the senile plaques in the brains of patients with Alzheimer's disease, is cytotoxic to neurons and has a central role in the pathogenesis of the disease. Previous studies have suggested that oxidative stress is involved in the mechanisms of Aβ‐induced neurotoxicity in vitro. In the present study, we examined whether oxidative stress contributes to learning and memory deficits caused by continuous intracerebroventricular infusion of Aβ‐(1–42). In the Aβ‐(1–42)‐infused rats, spontaneous alternation behaviour in a Y‐maze and spatial memory in a water maze task were significantly impaired, as compared with Aβ‐(40–1)‐infused control rats. The retention of passive avoidance learning was also significantly impaired by treatment with Aβ‐(1–42). Potent antioxidants idebenone and α‐tocopherol prevented the behavioural deficits in Y‐maze and water maze, but not passive avoidance, tasks in Aβ‐(1–42)‐infused rats when they were repeatedly administered by mouth once a day from 3 days before the start of Aβ infusion to the end of behavioural experiments. Lipid peroxide levels in the hippocampus and cerebral cortex of Aβ‐(1–42)‐infused rats did not differ from those in control animals, and neither idebenone nor α‐tocopherol affected the lipid peroxide levels. These results suggest that treatment with antioxidants such as idebenone and α‐tocopherol prevents learning and memory deficits caused by Aβ.