[Experimental techniques for developing new drugs acting on dementia (10)--Alzheimer's disease animal model induced by beta-amyloid protein].
To develop an animal model of Alzheimer's disease, beta-amyloid protein was infused into the rat cerebral ventricle for 14 days using a mini-osmotic pump. The performance of some memory tasks in the beta-amyloid protein-treated rats was impaired. Long-term potentiation in the hippocampus was impaired in beta-amyloid-infused rats. The impairment of memory under the infusion could be recovered by two cognitive enhancer drugs. Choline acetyltransferase activity significantly decreased in the frontal cortex and hippocampus but glial fibrillary acidic protein immunoreactivity increased in the cortex both immediately and 2 weeks after cessation of the infusion. Ciliary neurotrophic factor contents in several brain areas in beta-amyloid-infused rat significantly increased. Substance P and microtubule-associated protein, which play an important role in neuronal transmission and construction of neuronal cells, respectively, decreased. Moreover, the release of acetylcholine and dopamine from the cortex/hippocampus and striatum, respectively, in the beta-amyloid-infused rats after depolarization was smaller than that from the control rats. These results suggest that beta-amyloid protein induced dysfunction of the central nervous system in vivo, and that the animal could be used as a model of Alzheimer's disease.
Nitta
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A
Laboratory of Molecular Biology, Gifu Pharmaceutical University, Japan.
Nabeshima
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T
D000544:Alzheimer Disease / Q000139:chemically induced; D016229:Amyloid beta-Peptides / Q000008:administration & dosage; D000818:Animals; D001284:Atrophy; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D008868:Microtubule Proteins / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013373:Substance P / Q000378:metabolism
D016229:Amyloid beta-Peptides; D008868:Microtubule Proteins; D018377:Neurotransmitter Agents; D013373:Substance P; D002795:Choline O-Acetyltransferase