Late-life environmental enrichment preserves short-term memory and may attenuate microglia in male APP/PS1 mice

Abstract

Environmental enrichment (EE) has been consistently reported to enhance cognitive function in mouse models of neuropathology. Microglia, implicated in Alzheimer's disease pathology, may mediate this effect. The aim of the present study was to investigate the effect of EE on cognitive function and microglia in mouse models of aging and amyloidosis. Male wild-type (Wt) and APP/PS1 mice were randomly assigned to standard housing (SH) or EE from 12 to 18 months of age. Spatial memory testing was performed using the Y and Barnes maze. Immunohistochemical analysis of Aβ load, Iba1 and CD-68-labeled (phagocytic-type) microglia was examined between conditions. EE from 12 months of age was associated with improved short-term memory performance in APP/PS1 mice, despite no reductions to Aβ load. APP/PS1 mice in SH had significantly increased microglia occupying the neocortex and hippocampus (p = 0.02; p = 0.004, respectively) relative to Wt animals. Microglia labeling was not statistically different between EE-exposed APP/PS1 compared to Wt mice, indicating that EE may attenuate the increased microglial load in aging APP/PS1 mice. APP/PS1 mice from EE had significantly (p = 0.01) higher colocalization of Iba1 and CD-68 labeling, indicative of increased phagocytic microglia compared to mice from SH. The findings of the present study suggest that EE after substantial brain amyloidosis, has the potential to preserve domains of cognitive function, while having no effect on Aβ deposition. The current study demonstrates that EE may attenuate microglia in aging APP/PS1 mice, and may promote alterations in cellular phenotype.