Selective improvement of cognitive function in adult and aged APP/PS1 transgenic mice by continuous non-shock treadmill exercise.

Exercise may contribute to prevention of the cognitive decline and delay the onset of the Alzheimer's disease (AD). We evaluated the effects of continuous non-shock treadmill exercise in adult and aged male APP/PS1 double mutant transgenic mice. Adult (7-8 month-old) and aged (24 month-old) male APP/PS1 transgenic and wild-type mice were randomly assigned to either sedentary or exercise groups. The exercise program included a one-week treadmill acclimatization to adapt to the novel environment. After acclimation, mice ran on a treadmill 5 days/week until sacrificed for pathological analyses. During exercise training, no tail shock was used in the exercise paradigm; only gentle tail touching was used to induce the mice to run, to minimize the stress otherwise associated with treadmill exercise. We found that the exercise program selectively improved the spatial learning and memory associated with an increase in both cholinergic neurons in the medial septum (MS)/vertical diagonal band (VDB) and serotonergic neurons in the raphe nucleus of aged APP/PS1 transgenic mice. In adult APP/PS1 transgenic mice, the exercise paradigm increased exploratory activity and reduced anxiety with an associated increase in numbers of serotonergic neurons in the raphe nucleus. In addition, the exercise paradigm also reduced amyloid-β peptide (Aβ) levels and microglia activation, but not enough to reduce the plaque loading in the hippocampus of the APP/PS1 transgenic mice. Therefore, these findings suggest that there may exist an age-related difference in the effect of continuous non-shock treadmill exercise training on AD.