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ApoE and LDL receptor knockout mice display acquisition deficits in the Morris water maze

, : ApoE and LDL receptor knockout mice display acquisition deficits in the Morris water maze. Society for Neuroscience Abstracts 26(1-2): Abstract No -575 9

Much evidence now implicates apoE epsilon4 as a risk factor for Alzheimer's Disease. ApoE knockout (apoEKO) mice display impairments in the Morris Water Maze (MWM). Since apoE and the LDL receptor (LDLr), one of its main receptors, have been shown to be essential components of the brain lipid recycling system, we hypothesized that apoEKO and LDLrKO mice may exhibit similar behavioral deficits. We tested LDLrKO (7 months old) and apoEKO (3 and 9 months old) mice with their respective littermate controls (C57BL/6J) in the MWM. In Exp.1, mice were given 4 trials per day for 5 consecutive days in the standard MWM task having extramaze cues. On day 6, a probe trial was performed in which some salient cues were removed. Three months later, with extramaze cues returned, the mice were tested for platform recall. In Exp.2, mice were trained for 6 days in the MWM in which all extramaze cues were hidden by curtains. In Exp. 1, LDLrKO and both age groups of apoEKO (3 and 9 months) mice displayed significantly longer escape latencies and distances as compared to wild type mice, predominantly in the early days of training. When salient extramaze cues were removed, LDLrKO, apoEKO (3 months only) and their respective controls exhibited longer escape latencies and distances. All knockout and control mice appeared able to recall the platform location up to 3 months after their initial training. In Exp. 2, all groups of animals displayed somewhat longer latencies and distances as compared to Exp. 1, however, these differences were most pronounced in wild type mice. These experiments demonstrate that, in the presence of extramaze cues, wild type mice show enhanced acquisition in the MWM as compared to LDLrKO and apoEKO mice, as well as all groups performing in the absence of extramaze cues. LDLrKO and apoEKO mice seemed unable to derive this acquisitional benefit of the extramaze cues, but eventually used these cues to recall platform location as efficiently as controls. The similarities between apoEKO and LDLrKO mice suggest that a common mechanism may underlie the behavioral alterations.


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