Implanted cannula-mediated repetitive administration of Aβ25–35 into the mouse cerebral ventricle effectively impairs spatial working memory

Abstract: Amyloid β (Aβ) 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 Aβ 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 Aβ25–35 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 Aβ25–35-administered mice in a dose-dependent manner. Considering that the repetitive administration of a small dose of toxic Aβ 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 Aβ, 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. [Copyright &y& Elsevier]