Continuous infusion of beta-amyloid protein into the rat cerebral ventricle induces learning impairment and neuronal and morphological degeneration.
To investigate the toxicity of beta-amyloid protein, a component of the senile plaques in Alzheimer's disease, it was infused into the cerebral ventricle of rats for 14 days by a mini-osmotic pump. Performances in the water maze and passive avoidance tasks in beta-amyloid protein-treated rats were impaired. Choline acetyltransferase activity significantly decreased in the hippocampus both immediately and 2 weeks after the cessation of the infusion. However, the learning impairment was recoverable 2 weeks after cessation of the infusion. Both immediately and 2 weeks after the cessation of the infusion, glial fibrillary acidic protein immunoreactivity increased. Furthermore, beta-amyloid protein altered the staining in the nuclei of hippocampal cells for only 2 weeks after the cessation. These results suggest that beta-amyloid protein produces some damage in the central nervous system in vivo.
Nitta
A
A
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Tsuruma-cho, Showa-ku, Japan.
Fukuta
T
T
Hasegawa
T
T
Nabeshima
T
T
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D002795:Choline O-Acetyltransferase / Q000037:antagonists & inhibitors; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology; D005625:Frontal Lobe / Q000187:drug effects / Q000201:enzymology; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D009410:Nerve Degeneration / Q000187:drug effects; D010296:Parietal Lobe / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar
D016229:Amyloid beta-Peptides; D005904:Glial Fibrillary Acidic Protein; D002795:Choline O-Acetyltransferase