Enriched physical environment reverses spatial cognitive impairment of socially isolated APPswe/PS1dE9 transgenic mice before amyloidosis onset

Abstract

These results suggest that the enriched physical environment may serve as a nonpharmacological intervention for delaying the onset of AD accompanied with social isolation.

Transgenic Mouse Models as Tools for Understanding How Increased Cognitive and Physical Stimulation Can Improve Cognition in Alzheimer’s Disease

“…Increases have been seen following both exercise [ 21, 23, 32 ] and EE [ 44, 88, 133, 139–142 ]. Other studies applying EE as a preventative intervention using indirect measures of neurogenesis have shown similar increases [ 40, 42, 43, 90, 134, 135, 138 ]. Two groups using EE interventions did not observe enhanced neurogenesis [ 29, 133 ].…”

“…EE reproducibly improves performance in MWM in a diverse range of transgenic models [ 29, 36–46 ], with one exception [ 47 ]. Improvements were also seen in short-term memory tasks including the Y-maze [ 40 ], and novel object recognition [ 37, 42, 45, 48, 49 ]. Interventions applied after first report of cognitive impairment also positively impact on the phenotype of transgenic fAD mouse models.…”

“…Comparisons of exercise and EE-induced changes on amyloid pathology between studies is difficult due to methodological differences in not only measurement of markers but also between dose and timing of the lifestyle intervention. However, even if a similar EE paradigm is applied to the same model, the APP/PS1 mouse, for approximately the same amount of time, studies have shown Aβ increases [ 38, 89 ], no changes [ 40 ] and decreases [ 87, 88, 96 ]. Studies scrutinising different timing of intervention within the same model and importantly same laboratory, are helpful to shed insight on how these factors change the ability of exercise or EE to elicit cognitive benefits along with changes in pathology.…”

“…In general, both exercise and EE interventions have been shown to also slow the progression of neuronal death in fAD mouse models. Following exposure to preventative EE, decreased apoptotic cells [ 40, 46 ], reductions in levels of pro-apoptotic factors and increased pro-survival markers have been observed in fAD mice [ 40, 41, 142, 145 ]. A similar trend has been seen for exercise interventions applied before cognitive decline [ 146 ].…”

“…With regards to cognitive performance, studies describing effects of interventions on astrocyte and microglia are too inconsistent to draw conclusions [ 21, 37, 47, 49, 105, 142 ]. However, it seems decreased cytokines corresponded relatively well to improved cognition following preventative EE [ 40, 49, 142 ] except for one study [ 36 ]. In summary, the effects of lifestyle interactions on glial cells are unclear.…”