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

Marina Yamada, Tomohiro Chiba, Jumpei Sasabe, Mikiro Nawa, Hirohisa Tajima, Takako Niikura, Kenzo Terashita, Sadakazu Aiso, Yoshiko Kita, Masaaki Matsuoka, Ikuo Nishimoto

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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.

Original languageEnglish
Pages (from-to)139-146
Number of pages8
JournalBehavioural Brain Research
Volume164
Issue number2
DOIs
Publication statusPublished - 2005 Nov 7

Keywords

  • Alzheimer's disease
  • Amyloid beta (Aβ)
  • Implanted cannula
  • Spontaneous alternation behavior
  • Y-maze test

ASJC Scopus subject areas

  • Behavioral Neuroscience

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    Yamada, M., Chiba, T., Sasabe, J., Nawa, M., Tajima, H., Niikura, T., Terashita, K., Aiso, S., Kita, Y., Matsuoka, M., & Nishimoto, I. (2005). Implanted cannula-mediated repetitive administration of Aβ25-35 into the mouse cerebral ventricle effectively impairs spatial working memory. Behavioural Brain Research, 164(2), 139-146. https://doi.org/10.1016/j.bbr.2005.03.026