title: Human apoE targeted replacement mouse lines: h-apoE4 and h-apoE3 mice differ on spatial memory performance and avoidance behavior.
abstract: Apolipoprotein E4 (apoE4), one of the three most common human apoE (h-apoE) isoforms, is a major genetic risk factor for Alzheimer's disease and for cognitive deficits associated with aging. The biological mechanisms involving apoE in learning and memory processes are unclear. A potential isoform-dependent effect of h-apoE on cognitive performance was studied in gene-targeted mice, which show physiological expression levels and distribution of h-apoE3 or h-apoE4. Male and female h-apoE3 and h-apoE4, apoE-deficient and C57BL/6J mice (4-5 months) were subjected to tasks evaluating spatial memory and avoidance conditioning. Female h-apoE4 mice did not detect changes in the spatial configuration of objects as opposed to female h-apoE3 mice. Female h-apoE3 mice failed to improve their performance during training in a reference memory version of the spatial water-maze task, but performed well during the probe trial 24 h after the last training trial. Memory retention performances of h-apoE4 mice were impaired during this probe trial. Both h-apoE3 and h-apoE4 mice did not improve their performance in a water-maze delayed matching to place task. Finally, h-apoE3 mice showed mild perturbations in a Y-maze active avoidance task, whereas both h-apoE mouse lines performed well in a passive avoidance task. Thus, spatial memory performances appeared particularly sensitive to h-apoE-isoform-dependent effects. Deficits occurred predominantly in female h-apoE4 mice, which support the hypothesis that humans carrying h-apoE4, especially women, have impaired spatial memory compared to those carrying h-apoE3.
authors.affiliation: Laboratoire de Neurosciences Comportementales et Cognitives, Université Louis Pasteur, CNRS-UMR 7521, IFR 37, 12 rue Goethe, 67000 Strasbourg, France.
authors.forename: Jeannette
authors.initials: J
authors.lastname: Grootendorst
authors.forename: Alexandra
authors.initials: A
authors.lastname: Bour
authors.forename: Elise
authors.initials: E
authors.lastname: Vogel
authors.forename: Christian
authors.initials: C
authors.lastname: Kelche
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Sullivan
authors.forename: Jean-Cosme
authors.initials: JC
authors.lastname: Dodart
authors.forename: Kelly
authors.initials: K
authors.lastname: Bales
authors.forename: Chantal
authors.initials: C
authors.lastname: Mathis
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001362:Avoidance Learning / Q000502:physiology*; D003214:Conditioning, Classical / Q000502:physiology; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D018390:Gene Targeting; D005838:Genotype; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D012737:Sex Factors; D013037:Spatial Behavior / Q000502:physiology*
chemical_list: D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D020033:Protein Isoforms