Effects of environmental enrichment in a mouse model of Alzheimer's pathology

Objective Environmental enrichment (EE) has been proposed to reduce the risk of developing dementia in conditions such as Alzheimer’s disease (AD). The current project investigates the potential of different forms of later-life EE to ameliorate cognitive deterioration in ageing in wildtype (WT) mice as well as in a transgenic model (APP/PS1) of early-stage AD. Method Male transgenic (APPswe, PSEN1dE9) and WT mice entered differential housing from 6 [[unable to display character: –]] 12 months of age. Mice entered standard (SH) or EE housing. EE housing comprised a cage double the size of the SH cage, with various enrichment objects. A sub-set of EE mice (EE+) received additional stimulation by spending several hours a week in a larger cage with novel objects. Working memory (Y maze) was tested at 6 months, before entering differential housing, and at 9 and 12 months. At 12 months, mice were also tested for their long-term memory function on the Barnes maze. Results At 6 months, APP/PS1 mice demonstrated inferior Y maze performance compared to WT mice (n = 75, p < .001). After 3 months of differential housing, WT performance declined to the level of TG mice, and a combined effect of housing and genotype on Y maze performance was detected (p = .01). Post-hoc tests demonstrated that WT mice exhibited similar levels of performance regardless of housing condition, however TG EE mice demonstrated improved Y maze performance compared to SH mice (p < .01). After 6 months of differential housing, this effect dissipated (p = .76). Significantly longer latency on the Barnes maze was demonstrated by TG mice (p = .01). Housing condition did not predict long-term memory function on the Barnes maze in TG mice, however, WT animals exposed to EE made less errors on the Barnes maze than those in SH (p = .03). Conclusions The results indicate that EE confers differential beneficial effects to cognitive function. The results also suggest there is no additive effect of more complex, novel stimulation on memory function above that of standard EE. Results from cognitive testing data will be correlated with pathological brain alterations, including β-Amyloid plaque load and synaptic alterations