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
- 1 January 1999
- journal article
- research article
- Published by Wiley in European Journal of Neuroscience
- Vol. 11 (1), 83-90
- https://doi.org/10.1046/j.1460-9568.1999.00408.x
Abstract
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.Keywords
This publication has 60 references indexed in Scilit:
- Oxidative Stress Hypothesis in Alzheimer's DiseaseFree Radical Biology & Medicine, 1997
- Mechanisms of Neuronal Degeneration in Alzheimer's DiseaseNeuron, 1996
- Dysfunction of Cholinergic and Dopaminergic Neuronal Systems in β‐Amyloid Protein‐Infused RatsJournal of Neurochemistry, 1996
- Changes in ciliary neurotrophic factor content in the rat brain after continuous intracerebroventricular infusion of β-amyloid(1–40) proteinNeuroscience Letters, 1995
- β-Amyloid Peptide Free Radical Fragments Initiate Synaptosomal Lipoperoxidation in a Sequence-Specific Fashion: Implications to Alzheimer′s DiseaseBiochemical and Biophysical Research Communications, 1994
- Vitamin E Prevents the Place Learning Deficit and the Cholinergic Hypofunction Induced by AF64AExperimental Neurology, 1994
- Implants containing β-amyloid protein are not neurotoxic to young and old rat brainNeurobiology of Aging, 1992
- Vitamin E protects nerve cells from amyloid βprotein toxicityBiochemical and Biophysical Research Communications, 1992
- Neurotrophic and Neurotoxic Effects of Amyloid β Protein: Reversal by Tachykinin NeuropeptidesScience, 1990
- Stimulation of nerve growth factor synthesis/secretion by 1,4‐benzoquinone and its derivatives in cultured mouse astroglial cellsFEBS Letters, 1990