Implanted cannula-mediated repetitive administration of Abeta25-35 into the mouse cerebral ventricle effectively impairs spatial working memory

Behav Brain Res. 2005 Nov 7;164(2):139-46. doi: 10.1016/j.bbr.2005.03.026.

Abstract

Amyloid beta (Abeta) is closely related to the onset of Alzheimer's disease (AD). To construct AD animal models, a bolus administration of a large dose of toxic Abeta into the cerebral ventricles of rodents has been performed in earlier studies. In parallel, a continuous infusion system via an osmotic pump into the cerebral ventricle has been developed to make a rat AD model. In this study, we developed a mouse AD model by repetitive administration of Abeta25-35 via a cannula implanted into the cerebral ventricle. Using this administration system, we reproducibly constructed a mouse with impaired spatial working memory. In accordance with the occurrence of the abnormal mouse behavior, we found that the number of choline acetyltransferase (ChAT)-positive neurons was reduced in paraventricular regions of brains of Abeta25-35-administered mice in a dose-dependent manner. Considering that the repetitive administration of a small dose of toxic Abeta via an implanted cannula leads to a brain status more resembling that of the AD patients than a bolus injection of a large dose of Abeta, and therapeutic as well as toxic agents are able to be repeatedly and reliably administered via an implanted cannula, we concluded that the implanted cannula-bearing AD mouse model is useful for development of new AD therapy.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Alzheimer Disease / chemically induced*
  • Alzheimer Disease / physiopathology*
  • Amyloid beta-Peptides / administration & dosage*
  • Animals
  • Choline O-Acetyltransferase / drug effects
  • Choline O-Acetyltransferase / metabolism
  • Disease Models, Animal*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Exploratory Behavior / drug effects
  • Injections, Intraventricular
  • Maze Learning / drug effects
  • Memory, Short-Term / drug effects*
  • Mice
  • Neurons / drug effects
  • Neurons / enzymology
  • Paraventricular Hypothalamic Nucleus / drug effects
  • Paraventricular Hypothalamic Nucleus / enzymology*
  • Peptide Fragments / administration & dosage*
  • Reproducibility of Results
  • Space Perception / drug effects
  • Spatial Behavior / drug effects*

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • amyloid beta-protein (25-35)
  • Choline O-Acetyltransferase