Alzheimer's disease animal models induced by continuous infusion of ß-amyloid protein and anti-nerve growth factor antibody

Toshitaka Nabeshima, Akio Itoh

Research output: Contribution to journalReview article

7 Citations (Scopus)

Abstract

Alzheimer's disease (AD) is characterized by the presence of senile plaques and neurofibrillary tangles in the brain. The core of these plaques consists of ß-amyloid protein. In AD patients, learning and memory are impaired with a concomitant loss of the cholinergic neurons. Numerous investigators have reported the toxicity of ß-amyloid protein in vitro; however, no direct evidence that ß-amyloid protein is responsible for cholinergic denervation and memory impairment in vivo has been obtained. Nerve growth factor (NGF) is well known as a trophic factor for central cholinergic neurons involved in cell survival and maintenance. The relationship between NGF deficiency and the cholinergic denervation in AD has not been established. Therefore, we investigated whether memory impairment and neuronal dysfunction were induced after continuous infusion of ß-amyloid protein (1-40 amino acid residue) or an active Fab' fragment of anti-NGF antibody into the cerebral ventricles, or direct infusion of anti-NGF monoclonal or polyclonal antibody into the septum, of adult rats. Learning and memory in the habituation, Y-maze, water maze and passive avoidance tasks were impaired by the infusion of ß-amyloid protein (300 pmol/day) into the cerebral ventricle of rats. In these animals, a decrease in the levels of choline acetyltransferase (ChAT) activity and deposition of ß-amyloid protein in the frontal cortex and hippocampus were observed. The results of in vivo microdialysis study showed that the nicotine-stimulated release of acetylcholine and dopamine was significantly lower in ß-amyloid protein-treated rats than in control rats. In an electrophysiological study of the hippocampal CA1, the response to nicotine in ß-amyloid protein-treated rats was also impaired consistent with the results of the microdialysis study, suggesting.

Original languageEnglish
Pages (from-to)229-255
Number of pages27
JournalReviews on Heteroatom Chemistry
Volume16
Publication statusPublished - 01-12-1997
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Inorganic Chemistry

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