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Comparative studies using the Morris water maze to assess spatial memory deficits in two transgenic mouse models of Alzheimer's disease.
Clin Exp Pharmacol Physiol 2014; 41(10):798-806CE

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 coexpressing the 'Swedish' mutation of amyloid precursor protein (APPSwe) and the presenillin 1 (PS1) 'dE9' mutation were assessed in the MWM at mean ages of 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 7.25 months of age. In 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 21 months of age. There were no significant deficits in spatial memory retention up to 21 months of age and β-amyloid deposits were not present in brain sections up to 24 months of age. These 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.

Authors+Show Affiliations

Centre for Integrated Preclinical Drug Development, The University of Queensland, Brisbane, Qld, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25115283

Citation

Edwards, Stephen R., et al. "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 & Physiology, vol. 41, no. 10, 2014, pp. 798-806.
Edwards SR, Hamlin AS, Marks N, et al. Comparative studies using the Morris water maze to assess spatial memory deficits in two transgenic mouse models of Alzheimer's disease. Clin Exp Pharmacol Physiol. 2014;41(10):798-806.
Edwards, S. R., Hamlin, A. S., Marks, N., Coulson, E. J., & Smith, M. 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 & Physiology, 41(10), pp. 798-806. doi:10.1111/1440-1681.12277.
Edwards SR, et al. Comparative Studies Using the Morris Water Maze to Assess Spatial Memory Deficits in Two Transgenic Mouse Models of Alzheimer's Disease. Clin Exp Pharmacol Physiol. 2014;41(10):798-806. PubMed PMID: 25115283.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative studies using the Morris water maze to assess spatial memory deficits in two transgenic mouse models of Alzheimer's disease. AU - Edwards,Stephen R, AU - Hamlin,Adam S, AU - Marks,Nicola, AU - Coulson,Elizabeth J, AU - Smith,Maree T, PY - 2014/04/15/received PY - 2014/06/05/revised PY - 2014/06/08/accepted PY - 2014/8/14/entrez PY - 2014/8/15/pubmed PY - 2015/7/2/medline KW - APPSwe YAC mice KW - APPSwe/PS1dE9 mice KW - Alzheimer's disease KW - Morris water maze KW - cognitive deficits KW - spatial memory KW - transgenic mouse models KW - β-amyloid SP - 798 EP - 806 JF - Clinical and experimental pharmacology & physiology JO - Clin. Exp. Pharmacol. Physiol. VL - 41 IS - 10 N2 - 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 coexpressing the 'Swedish' mutation of amyloid precursor protein (APPSwe) and the presenillin 1 (PS1) 'dE9' mutation were assessed in the MWM at mean ages of 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 7.25 months of age. In 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 21 months of age. There were no significant deficits in spatial memory retention up to 21 months of age and β-amyloid deposits were not present in brain sections up to 24 months of age. These 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. SN - 1440-1681 UR - https://www.unboundmedicine.com/medline/citation/25115283/Comparative_studies_using_the_Morris_water_maze_to_assess_spatial_memory_deficits_in_two_transgenic_mouse_models_of_Alzheimer's_disease_ L2 - https://doi.org/10.1111/1440-1681.12277 DB - PRIME DP - Unbound Medicine ER -