Jpn. J. Pharmacol. 73 (1), 51-57 (1997)

Continuous Infusion of beta-Amyloid Protein into the Rat Cerebral Ventricle Induces Learning Impairment and Neuronal and Morphological Degeneration

Atsumi Nitta (1,2), Taneo Fukuta (1), Takaaki Hasegawa (1) and Toshitaka Nabeshima (1,*)

(1) Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Tsuruma-cho 65, Showa-ku, Nagoya 466, Japan
(2) Laboratory of Molecular Biology, Gifu Pharmaceutical University, 5-6-1 Mitahora-Higashi, Gifu 502, Japan
(*) To whom correspondence should be addressed.

Abstract: 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.

Keywords: Amyloid protein, Alzheimer's disease, Learning and memory, Cholinergic neuron, Glial fibrillary acidic protein