Mid‐life environmental enrichment increases synaptic density in CA1 in a mouse model of Aβ‐associated pathology and positively influences synaptic and cognitive health in healthy ageing

Abstract

Early-life cognitive enrichment may reduce the risk of experiencing cognitive deterioration and dementia in later-life. However, an intervention to prevent or delay dementia is likely to be taken up in mid to later-life. Hence, we investigated the effects of environmental enrichment in wildtype mice and in a mouse model of Aβ neuropathology (APP /PS1 ) from 6 months of age. After 6 months of housing in standard laboratory cages, APP /PS1 (n = 27) and healthy wildtype (n = 21) mice were randomly assigned to either enriched or standard housing. At 12 months of age, wildtype mice showed altered synaptic protein levels and relatively superior cognitive performance afforded by environmental enrichment. Environmental enrichment was not associated with alterations to Aβ plaque pathology in the neocortex or hippocampus of APP /PS1 mice. However, a significant increase in synaptophysin immunolabeled puncta in the hippocampal subregion, CA1, in APP /PS1 mice was detected, with no significant synaptic density changes observed in CA3, or the Fr2 region of the prefrontal cortex. Moreover, a significant increase in hippocampal BDNF was detected in APP /PS1 mice exposed to EE, however, no changes were detected in neocortex or between Wt animals. These results demonstrate that mid to later-life cognitive enrichment has the potential to promote synaptic and cognitive health in ageing, and to enhance compensatory capacity for synaptic connectivity in pathological ageing associated with Aβ deposition.

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

“…However, synaptic proteins SYP and PSD‐95 are increased in the hippocampus of GR+EE mice relative to those of GR+SE mice. Similarly, previous studies on AD transgenic mice or wild‐type mice also showed an improving effect of EE on hippocampal expression of genes/proteins related to synaptic plasticity. Together, these results suggest that the spatial cognition reserved by EE is associated with increased experience‐dependent synaptogenesis in young APP/PS1 mice prior to the amyloidosis onset.…”

“…We demonstrated that 8 weeks of exposure to EE improves spatial learning and memory of young APP/PS1 mice housed in a standard environment. In line with this, previous studies have revealed that enrichment has a beneficial effect on cognitive function of various AD mouse models, such as APPswe transgenic mice, APP23 transgenic mice, Tg2576 mice, APPswe/PS1dE9 mice, and PS1/PDAPP mice . However, effects of EE on the levels of Aβ in AD transgenic mice are controversial, showing three different results: decreases, increases, and no changes …”

Environmental enrichment and exercise are better than social enrichment to reduce memory deficits in amyloid beta neurotoxicity

“…Environmental enrichment (EE) has been suggested as an efficient strategy to treat human AD and AD-like animal models (12,13). EE has potential to ameliorate deficits resulting from the administration of Aβ protein oligomers (14,15). However, EE as used in animal research usually includes other variables than perception and memorization, which make it difficult to determine the nature of its eventually favorable effects.…”

The BDNF Val66Met Polymorphism Modulates Resilience of Neurological Functioning to Brain Ageing and Dementia: A Narrative Review

“…In animal studies, brain BDNF is increased in the hippocampus and cerebral cortex following exercise [88], as well as following environmental enrichment which also promotes physical activity (e.g., [89][90][91]). Blocking BDNF action inhibits the exercise-mediated increase in synaptic proteins [92].…”