Protective effects of
and alpha-tocopherol on beta-amyloid-(1-42)-induced learning and memory
deficits in rats: implication of oxidative stress in beta-amyloid-induced
neurotoxicity in vivo.
Yamada K, Tanaka T, Han D,
Senzaki K, Kameyama T,
Department of Neuropsychopharmacology and Hospital Pharmacy,
School of Medicine, Japan.
Eur J Neurosci 1999 Jan;11(1):83-90
Amyloid beta-peptide (A beta), 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 A beta-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 A
beta-(1-42). In the A beta-(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 A beta-(40-1)-infused control rats.
The retention of passive avoidance learning was also significantly impaired by
treatment with A beta-(1-42). Potent antioxidants idebenone and
alpha-tocopherol prevented the behavioural deficits in Y-maze and water maze,
but not passive avoidance, tasks in A beta-(1-42)-infused rats when they were
repeatedly administered by mouth once a day from 3 days before the start of A
beta infusion to the end of behavioural experiments. Lipid peroxide levels in
the hippocampus and cerebral cortex of A beta-(1-42)-infused rats did not
differ from those in control animals, and neither idebenone nor alpha-tocopherol
affected the lipid peroxide levels. These results suggest that treatment with
antioxidants such as idebenone and alpha-tocopherol prevents learning
and memory deficits caused by A beta.