Locomotor behaviour, emotionality, and cognition in the 3xTg-AD mouse model of Alzheimer's disease: A cross-sectional study

Abstract

The triple transgenic (3xTg-AD) mouse model of Alzheimer’s disease (AD) possesses three transgenes that lead to the development of amyloid-beta (A?) plaques (APPswe, PS1M146V) and neurofibrillary tangles (and tauP301L) (Oddo et al., 2003b). Although the neuropathology of these mice has been extensively studied (Sy et al., 2011), less research has been done to investigate their working memory, emotionality, and locomotor-related behaviour. Using a cross-sectional design, male and female 3xTg-AD mice were compared to control mice (B6129SF2/J) at five ages (2-, 6-, 9-, 12-, and 15-months of age) on a battery of five tests designed to measure: anxiety- and locomotor-related behaviours (open field [OF], elevated plus maze [EPM]); depression (forced swim test [FST]); motor coordination and motor learning (rotarod); and working and reference memory (8-arm radial maze [RAM]). Additionally, the brain tissue of male and female 3xTg-AD and control mice at 2- and 15-months of age was analyzed for the presence of A? plaques and human tauP301L. 3xTg-AD mice were found to travel less and freeze more in both the OF and the EPM, engage in fewer bouts of immobility in the FST, have a longer latency to fall on the rotarod, and make more working and reference memory errors in the RAM than controls. There was no effect of age on performance in any of the tests. Intracellular A? plaques and limited human tau were present in the brain tissue of 2-month old 3xTg-AD mice. At 15-months of age, the brain tissue of 3xTg-AD mice showed extensive intra- and extracellular A? plaques as well as tauP301L staining. The presence of intracellular A? at 2-months of age supports the behavioural differences observed in the 3xTg-AD mice at 2-months of age. However, the lack of progressive behavioural change does not match the increase in neuropathology seen in the brains of the 15-month old 3xTg-AD mice. The results of the present study suggest that while the 3xTg-AD mice display similar neuropathology and some of the behavioural differences seen in individuals with AD, they also exhibit contradictory behaviours; findings that should be taken into consideration for future researchers using 3xTg-AD mice.