Memory impairment and neuronal dysfunction induced by beta-amyloid protein in rats.
Alzheimer's disease (AD) is characterized by the presence of senile plaques. The core of the plaque consists of beta-amyloid protein. In AD patients, learning and memory are impaired with a concomitant loss of the cholinergic marker enzyme, choline acetyltransferase (ChAT). However, direct evidence that beta-amyloid protein is related to the impairment of learning and memory has not been demonstrated. In this study, we investigated whether memory impairment and neuronal dysfunction were produced after 2 weeks continuous infusion of beta-amyloid protein (3, 30 and 300 pmol/day) into the cerebral ventricles in adult rats. To investigate the ability of learning and memory in beta-amyloid protein-treated rats, water maze and passive avoidance tasks were carried out. The performance of both tasks in beta-amyloid protein-treated rats was impaired. ChAT activity in the frontal cortex (3 and 30 pmol/day) and hippocampus (300 pmol/day) significantly decreased. These results suggest that beta-amyloid protein is related to the impairment of learning and memory, and neurodegeneration, and that beta-amyloid protein-treated rats could be used as an animal model for AD.
Nabeshima
T
T
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Japan.
Nitta
A
A
D000110:Acetylcholinesterase / Q000172:deficiency*; D000544:Alzheimer Disease; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000633:toxicity*; D000818:Animals; D001362:Avoidance Learning; D001923:Brain Chemistry; D002795:Choline O-Acetyltransferase / Q000172:deficiency*; D003342:Corpus Striatum / Q000737:chemistry; D004195:Disease Models, Animal; D005625:Frontal Lobe / Q000737:chemistry; D006624:Hippocampus / Q000737:chemistry; D015918:Infusion Pumps, Implantable; D007276:Injections, Intraventricular; D007859:Learning Disabilities / Q000139:chemically induced*; D008297:Male; D018782:Maze Learning; D008569:Memory Disorders / Q000139:chemically induced*; D009419:Nerve Tissue Proteins / Q000172:deficiency*; D010296:Parietal Lobe / Q000737:chemistry; D010446:Peptide Fragments / Q000008:administration & dosage / Q000138:chemical synthesis / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
D016229:Amyloid beta-Peptides; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase