title: Implanted cannula-mediated repetitive administration of Abeta25-35 into the mouse cerebral ventricle effectively impairs spatial working memory.
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.
authors.affiliation: Department of Pharmacology, KEIO University School of Medicine, 35 Shinanomachi, Tokyo 160-8582, Japan.
authors.forename: Marina
authors.initials: M
authors.lastname: Yamada
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Chiba
authors.forename: Jumpei
authors.initials: J
authors.lastname: Sasabe
authors.forename: Mikiro
authors.initials: M
authors.lastname: Nawa
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Tajima
authors.forename: Takako
authors.initials: T
authors.lastname: Niikura
authors.forename: Kenzo
authors.initials: K
authors.lastname: Terashita
authors.forename: Sadakazu
authors.initials: S
authors.lastname: Aiso
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Kita
authors.forename: Masaaki
authors.initials: M
authors.lastname: Matsuoka
authors.forename: Ikuo
authors.initials: I
authors.lastname: Nishimoto
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced* / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage*; D000818:Animals; D002795:Choline O-Acetyltransferase / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005106:Exploratory Behavior / Q000187:drug effects; D007276:Injections, Intraventricular; D018782:Maze Learning / Q000187:drug effects; D008570:Memory, Short-Term / Q000187:drug effects*; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000201:enzymology*; D010446:Peptide Fragments / Q000008:administration & dosage*; D015203:Reproducibility of Results; D013028:Space Perception / Q000187:drug effects; D013037:Spatial Behavior / Q000187:drug effects*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D002795:Choline O-Acetyltransferase