Continuous infusion of beta-amyloid protein into the rat cerebral ventricle induces learning impairment and neuronal and morphological degeneration

Jpn J Pharmacol. 1997 Jan;73(1):51-7. doi: 10.1254/jjp.73.51.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / toxicity*
  • Animals
  • Avoidance Learning / drug effects*
  • Choline O-Acetyltransferase / antagonists & inhibitors
  • Corpus Striatum / drug effects
  • Corpus Striatum / enzymology
  • Frontal Lobe / drug effects
  • Frontal Lobe / enzymology
  • Glial Fibrillary Acidic Protein / analysis
  • Hippocampus / drug effects
  • Hippocampus / enzymology
  • Hippocampus / ultrastructure
  • Immunohistochemistry
  • Injections, Intraventricular
  • Male
  • Maze Learning / drug effects*
  • Nerve Degeneration / drug effects
  • Parietal Lobe / drug effects
  • Parietal Lobe / enzymology
  • Rats
  • Rats, Wistar


  • Amyloid beta-Peptides
  • Glial Fibrillary Acidic Protein
  • Choline O-Acetyltransferase