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Middle-aged human apoE4 targeted-replacement mice show retention deficits on a wide range of spatial memory tasks.

Publication ,  Journal Article
Bour, A; Grootendorst, J; Vogel, E; Kelche, C; Dodart, J-C; Bales, K; Moreau, P-H; Sullivan, PM; Mathis, C
Published in: Behav Brain Res
November 21, 2008

Apolipoprotein (apo) E4, one of three human apoE (h-apoE) isoforms, has been identified as a major genetic risk factor for Alzheimer's disease and for cognitive deficits associated with aging. However, the biological mechanisms involving apoE in learning and memory processes are unclear. A potential isoform-dependent role of apoE in cognitive processes was studied in human apoE targeted-replacement (TR) mice. These mice express either the human apoE3 or apoE4 gene under the control of endogenous murine apoE regulatory sequences, resulting in physiological expression of h-apoE in both a temporal and spatial pattern similar to humans. Male and female apoE3-TR, apoE4-TR, apoE-knockout and C57BL/6J mice (15-18 months) were tested with spatial memory and avoidance conditioning tasks. Compared to apoE3-TR mice, spatial memory in female apoE4-TR mice was impaired based on their poor performances in; (i) the probe test of the water-maze reference memory task, (ii) the water-maze working memory task and (iii) an active avoidance Y-maze task. Retention performance on a passive avoidance task was also impaired in apoE4-TR mice, but not in other genotypes. These deficits in both spatial and avoidance memory tasks may be related to the anatomical and functional abnormalities previously reported in the hippocampus and the amygdala of apoE4-TR mice. We conclude that the apoE4-TR mice provide an excellent model for understanding the mechanisms underlying apoE4-dependent susceptibility to cognitive decline.

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Published In

Behav Brain Res

DOI

ISSN

0166-4328

Publication Date

November 21, 2008

Volume

193

Issue

2

Start / End Page

174 / 182

Location

Netherlands

Related Subject Headings

  • Spatial Behavior
  • Retention, Psychology
  • Neurology & Neurosurgery
  • Middle Aged
  • Mice, Transgenic
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Memory
  • Maze Learning
 

Citation

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Bour, A., Grootendorst, J., Vogel, E., Kelche, C., Dodart, J.-C., Bales, K., … Mathis, C. (2008). Middle-aged human apoE4 targeted-replacement mice show retention deficits on a wide range of spatial memory tasks. Behav Brain Res, 193(2), 174–182. https://doi.org/10.1016/j.bbr.2008.05.008
Bour, Alexandra, Jeannette Grootendorst, Elise Vogel, Christian Kelche, Jean-Cosme Dodart, Kelly Bales, Pierre-Henri Moreau, Patrick M. Sullivan, and Chantal Mathis. “Middle-aged human apoE4 targeted-replacement mice show retention deficits on a wide range of spatial memory tasks.Behav Brain Res 193, no. 2 (November 21, 2008): 174–82. https://doi.org/10.1016/j.bbr.2008.05.008.
Bour A, Grootendorst J, Vogel E, Kelche C, Dodart J-C, Bales K, et al. Middle-aged human apoE4 targeted-replacement mice show retention deficits on a wide range of spatial memory tasks. Behav Brain Res. 2008 Nov 21;193(2):174–82.
Bour, Alexandra, et al. “Middle-aged human apoE4 targeted-replacement mice show retention deficits on a wide range of spatial memory tasks.Behav Brain Res, vol. 193, no. 2, Nov. 2008, pp. 174–82. Pubmed, doi:10.1016/j.bbr.2008.05.008.
Bour A, Grootendorst J, Vogel E, Kelche C, Dodart J-C, Bales K, Moreau P-H, Sullivan PM, Mathis C. Middle-aged human apoE4 targeted-replacement mice show retention deficits on a wide range of spatial memory tasks. Behav Brain Res. 2008 Nov 21;193(2):174–182.
Journal cover image

Published In

Behav Brain Res

DOI

ISSN

0166-4328

Publication Date

November 21, 2008

Volume

193

Issue

2

Start / End Page

174 / 182

Location

Netherlands

Related Subject Headings

  • Spatial Behavior
  • Retention, Psychology
  • Neurology & Neurosurgery
  • Middle Aged
  • Mice, Transgenic
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Memory
  • Maze Learning