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P4‐022: Swimming training‐to‐criterion and pre‐exposure to MWM are required for complete restoration of learning in APP transgenic mice carrying a mutation in Asp664
Author(s) -
Zhang Junli,
Gorostiza Olivia,
Tang Huidong,
Bredesen Dale E.,
Galvan Veronica
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.04.892
Subject(s) - morris water navigation task , genetically modified mouse , cognition , confounding , cohort , psychology , toxicity , neuroscience , phenotype , transgene , effects of sleep deprivation on cognitive performance , medicine , biology , genetics , gene
Background: Recent advances in developing transgenic mouse models of Alzheimer’s disease containing both tau and APP mutations have relied upon multiple pro-nuclear injections for their generation. Inevitably, this has produced uncertainties about the consistency of gene dosing and gene location. Therefore, we have developed the first 3rd generation mouse model of Alzheimer’s disease using a targeted knock in of human APP and tau mutations (see accompanying posters). A hallmark of AD-related neurodegeneration is diminished hippocampal function, manifesting in impaired spatial memory and learning capacity. Accordingly, this poster describes the assessment of such functions in PLB1triple mice. Methods: Working and reference memory were assessed in PLB1triple and wild type (WT) mice at 5 months of age using a radial arm water maze (RAWM) with a ‘trials-to-criterion’ protocol. Analyses also considered gender differences (WT: males, n 1⁄4 18; females, n 1⁄4 12. PLB1triple: males, n 1⁄4 20; females, n 1⁄4 25). Mice were required to find a submerged platform located at the extremity of one of eight arms (two consecutive trials with no more than a total of two errors), for three different consecutive platform locations. Results: The absence of any visual deficit was confirmed by equal performance by all groups in locating a visible platform. During acquisition, male PLB1triple mice required significantly more trials to complete all problems than their wild-type counterparts (P<0.05). This deficit was not observed in female mice, neither could any deficit be observed in female mice in any parameter investigated at this age. A male-specific deficit was also seen in the total number of errors made to complete all tasks (P<0.05), specifically a deficit in reference memory (with no effect observed in working memory). Male transgenic animals also displayed faster swimspeed than wild types (P<0.05). Conclusions: A deficit in memory is evident in triple transgenic mice at 5 months of age. Though the deficit described here is mild (and is in contrast to many of the aggressive transgenic models of AD available) it may provide a better reflection of early pathology of AD as a progressive neurodegenerative condition.