| Abstract No.: | A-C1090 |
| Country: | Canada |
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| Title: | COMPARISON OF SPECIES-TYPICAL AND SOCIAL BEHAVIOURS IN TWO DOUBLE-TRANSGENIC MOUSE MODELS OF ALZHEIMER’S DISEASE AT 12 MONTHS OF AGE |
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| Authors/Affiliations: | 1 Jacalynne Hernandez-Lee*; 1 Rhian Gunn; 1 Kevin Duffy; 1 Richard Brown;
1 Dalhousie University, Halifax, NS, Canada
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| Content: | Objectives: Rodent models have become indispensable for the study of genetic, neural and behavioural deficits of Alzheimer’s disease (AD). Many mouse models of AD are available (Eriksen & Janus 2007, Behav Genet, 37, 79) and differences in the background strain can be a source of behavioural variance in these mouse models. The aim of this project was to compare two double transgenic mouse models of AD and their wildtype littermate controls at 12 months of age in species-typical and social behaviours.
Materials and Methods: Two double transgenic mouse models of AD, B6C3-Tg(APPSwe,PSEN1dE9)85Dbo/J (APP+PS1dE9; JAX # 004462) and B6C3-Tg(APP695)3DboTg(PSEN1)5Dbo/J (APP695+PSEN1; JAX # 003378) and their wildtype (wt) littermate controls were compared in tests of anxiety (light/dark transition box), species-typical behaviour (nest building, food hoarding), social memory (social recognition, social transmission of food preference), olfactory learning and memory (habituation-dishabituation) and spatial learning and memory (Morris water maze) at 12 months of age. Congo red staining of amyloid beta plaques in the brain was conducted to compare the neuropathology of AD in the two mouse models.
Results: Both transgenic mouse models showed increased anxiety compared to their wt controls. The APP+PS1dE9 strain did not differ from their wt controls in nest building, however, the APP695+PSEN1 strain built poorer nests than their wt controls. The APP+PSEN1 transgenic mice and their wt littermates hoarded more food than the APP+PS1dE9 mice and their wt littermates, thus this appears to be a background strain effect. All mice showed sociability in the social recognition task, although none demonstrated a preference for social novelty. The APP+PS1dE9 mice and their wt littermates spent more time exploring novel odours than the APP695+PSEN1 mice and their wt littermates; transgenic mice explored the odours longer than wt mice. There was no difference in social transmission of food preference. The APP695+PSEN1 and their wt littermates ate more food overall than the APP+PS1dE9 and their wt littermates, and the APP695+PSEN1 transgenic mice at the most food overall. The APP+PS1dE9 strain and their wt littermates swam significantly slower, but performed better than the APP695+PSEN1 and their wildtype littermates in the acquisition, reversal, and probe trials of the Morris water maze. However, the APP+PS1dE9 strain did not demonstrate a reversal effect unlike the other mice. The APP+PS1dE9 transgenic strain showed more Congo red stained amyloid beta plaques in the hippocampus and cortex than the APP695+PSEN1 transgenic strain at 12 months of age.
Conclusion: Deficits in cognitive behaviour were found in the APP+PS1dE9 strain while deficits in species typical behaviour were found in the APP695+PSEN1 strain, suggesting that neurobehavioural deficits in transgenic mouse models of AD are due to an interaction between background strain and genes implicated in AD. However, AD patients suffer both cognitive deficits and deficits in everyday maintenance behaviour (Rockwood 2007, Int Psychogeriatr, 19, 147). These results are the first to compare cognitive and |
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