Protectiye 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

Research output: Contribution to journalArticle

194 Citations (Scopus)

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 cc-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.

Original languageEnglish
Pages (from-to)83-90
Number of pages8
JournalEuropean Journal of Neuroscience
Volume11
Issue number1
Publication statusPublished - 01-12-1999
Externally publishedYes

Fingerprint

Tocopherols
Memory Disorders
Amyloid
Oxidative Stress
Learning
Lipid Peroxides
Antioxidants
Intraventricular Infusions
Avoidance Learning
Water
Amyloid Plaques
Cerebral Cortex
Mouth
Hippocampus
Alzheimer Disease
Neurons
idebenone
Brain
Therapeutics

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

@article{dd18d95d0b554eacbe371025cbfce446,
title = "Protectiye 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",
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 cc-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.",
author = "Toshitaka Nabeshima",
year = "1999",
month = "12",
day = "1",
language = "English",
volume = "11",
pages = "83--90",
journal = "European Journal of Neuroscience",
issn = "0953-816X",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Protectiye effects of idebenone and α-tocopherol on β-amyloid-(1-42)-induced learning and memory deficits in rats

T2 - Implication of oxidative stress in β-amyloid-induced neurotoxicity in vivo

AU - Nabeshima, Toshitaka

PY - 1999/12/1

Y1 - 1999/12/1

N2 - 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 cc-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.

AB - 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 cc-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.

UR - http://www.scopus.com/inward/record.url?scp=0032898672&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032898672&partnerID=8YFLogxK

M3 - Article

C2 - 9987013

AN - SCOPUS:0032898672

VL - 11

SP - 83

EP - 90

JO - European Journal of Neuroscience

JF - European Journal of Neuroscience

SN - 0953-816X

IS - 1

ER -