PMID- 19464276
OWN - NLM
STAT- MEDLINE
DCOM- 20090914
LR  - 20191210
IS  - 1872-6240 (Electronic)
IS  - 0006-8993 (Linking)
VI  - 1280
DP  - 2009 Jul 14
TI  - Validation of Abeta1-40 administration into mouse cerebroventricles as an animal 
      model for Alzheimer disease.
PG  - 137-47
LID - 10.1016/j.brainres.2009.05.035 [doi]
AB  - Valid animal models for a specific human disease are indispensable for 
      development of new therapeutic agents. The conclusions drawn from animal models 
      largely depend on the validity of the model. Several studies have shown that 
      administration of Abeta into the brain causes some of the pathological events 
      observed in Alzheimer disease (AD). However, the validity of these models has not 
      fully been examined. In this present study, we further characterized and 
      validated Abeta1-40 injected mice as an animal model for AD, based on three major 
      criteria: face, construct and predictive validity. Intracerebroventricular 
      (i.c.v.) injection of Abeta1-40 into mice significantly impaired memory 
      acquisition, but not memory retrieval, which implies similarity to the episodic 
      anterograde memory deficit observed in the early stage of AD. 
      Electrophysiological assessment showed that i.c.v. administration of Abeta1-40 
      significantly attenuated hippocampal long-term potentiation. Treatment with 
      galantamine, a drug currently in clinical use for AD, significantly improved 
      cognitive dysfunction in this model. These results demonstrate that i.c.v. 
      injection of Abeta1-40 caused specific dysfunction of memory processes, which at 
      least partly fulfills three validity criteria for AD. Symptomatic and 
      pathophysiological similarities of this model to AD are quite important in 
      considering the usefulness of this animal model. This validated animal model 
      could be useful to develop and evaluate potential new drugs for AD.
FAU - Takeda, Shuko
AU  - Takeda S
AD  - Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka 
      University, Suita, Osaka, Japan.
FAU - Sato, Naoyuki
AU  - Sato N
FAU - Niisato, Kazue
AU  - Niisato K
FAU - Takeuchi, Daisuke
AU  - Takeuchi D
FAU - Kurinami, Hitomi
AU  - Kurinami H
FAU - Shinohara, Mitsuru
AU  - Shinohara M
FAU - Rakugi, Hiromi
AU  - Rakugi H
FAU - Kano, Masanobu
AU  - Kano M
FAU - Morishita, Ryuichi
AU  - Morishita R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Validation Study
DEP - 20090521
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Neurotoxins)
RN  - 0 (Nootropic Agents)
RN  - 0 (Peptide Fragments)
RN  - 0 (amyloid beta-protein (1-40))
RN  - 0D3Q044KCA (Galantamine)
SB  - IM
MH  - *Alzheimer Disease
MH  - Amyloid beta-Peptides/*administration & dosage
MH  - Animals
MH  - *Cerebral Ventricles
MH  - Cognition Disorders/drug therapy/physiopathology
MH  - *Disease Models, Animal
MH  - Galantamine/pharmacology
MH  - Hippocampus/drug effects/physiopathology
MH  - Injections, Intraventricular
MH  - Long-Term Potentiation/physiology
MH  - Male
MH  - Memory/drug effects/physiology
MH  - Memory Disorders/drug therapy/physiopathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neurotoxins/*administration & dosage
MH  - Nootropic Agents/pharmacology
MH  - Peptide Fragments/*administration & dosage
EDAT- 2009/05/26 09:00
MHDA- 2009/09/15 06:00
CRDT- 2009/05/26 09:00
PHST- 2009/03/19 00:00 [received]
PHST- 2009/05/08 00:00 [revised]
PHST- 2009/05/08 00:00 [accepted]
PHST- 2009/05/26 09:00 [entrez]
PHST- 2009/05/26 09:00 [pubmed]
PHST- 2009/09/15 06:00 [medline]
AID - S0006-8993(09)00955-X [pii]
AID - 10.1016/j.brainres.2009.05.035 [doi]
PST - ppublish
SO  - Brain Res. 2009 Jul 14;1280:137-47. doi: 10.1016/j.brainres.2009.05.035. Epub 
      2009 May 21.