Comparative studies using the Morris water maze to assess spatial memory deficits in two transgenic mouse models Of Alzheimer's disease

Edwards, Stephen R., Hamlin, Adam S., Marks, Nicola, Coulson, Elizabeth J. and Smith, Maree T. (2014) Comparative studies using the Morris water maze to assess spatial memory deficits in two transgenic mouse models Of Alzheimer's disease. Clinical and Experimental Pharmacology and Physiology, 41 10: 798-806. doi:10.1111/1440-1681.12277

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Author Edwards, Stephen R.
Hamlin, Adam S.
Marks, Nicola
Coulson, Elizabeth J.
Smith, Maree T.
Title Comparative studies using the Morris water maze to assess spatial memory deficits in two transgenic mouse models Of Alzheimer's disease
Journal name Clinical and Experimental Pharmacology and Physiology   Check publisher's open access policy
ISSN 0305-1870
1440-1681
Publication date 2014-10
Year available 2014
Sub-type Article (original research)
DOI 10.1111/1440-1681.12277
Open Access Status
Volume 41
Issue 10
Start page 798
End page 806
Total pages 9
Place of publication Richmond Australia
Publisher Wiley-Blackwell Publishing Asia
Collection year 2015
Language eng
Formatted abstract
Evaluation of the efficacy of novel therapeutics for potential treatment of Alzheimer's Disease (AD) requires an animal model that develops age-related cognitive deficits reproducibly between independent groups of investigators. Herein, we assessed comparative temporal changes in spatial memory function in two commercially available transgenic mouse models of AD, using the Morris water maze (MWM) incorporating both visible and hidden platform training. Individual cohorts of cDNA-based ‘line 85’-derived double transgenic mice co-expressing the ‘Swedish’ mutation of amyloid precursor protein (APPSwe) and the presenillin 1 (PS1) ‘dE9’ mutation were assessed in the MWM at mean ages 3.6, 9.3, and 14.8 months. We found significant deficits in spatial memory retention in APPSwe/PS1dE9 mice aged 3.6 months, and robust deficits in spatial memory acquisition and retention in APPSwe/PS1dE9 mice aged 9.3 months, with a further significant decline by age 14.8 months. β-amyloid deposits were present in brain sections by age 7.25 months. By contrast, MWM studies with individual cohorts (aged 4-21 months) of single transgenic genomic-based APPSwe mice expressing APPSwe on a yeast artificial chromosomal (YAC) construct, showed no significant deficits in spatial memory acquisition until age 21 months. There were no significant deficits in spatial memory retention up to age 21 months, and β-amyloid deposits were not present in brain sections up to age 24 months. Our data generated using comprehensive study designs show that APPSwe/PS1dE9 but not APPSwe YAC mice, appear to provide a suitably robust model of AD for efficacy assessment of novel AD treatments in development.
Keyword Alzheimer's disease (AD)
APPSwe/PS1dE9 mice
APPSwe YAC mice
β-Amyloid
Morris water maze
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2015 Collection
School of Pharmacy Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 3 times in Thomson Reuters Web of Science Article | Citations
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Created: Sat, 20 Sep 2014, 08:21:17 EST by Professor Maree Smith on behalf of Centre for Integrated Preclinical Drug Development