Environmental enrichment lessens cognitive decline in APP23 mice without affecting brain sirtuin expression

Area of Science:

• Neuroscience
• Alzheimer's Disease Research
• Animal Models

Background:

• Environmental enrichment (EE) is a promising non-pharmacological approach for Alzheimer's disease (AD).
• Its effects on cognitive decline and amyloid-beta (Aβ) pathology in AD mouse models require further elucidation.
• The role of sirtuins (SIRTs) as potential mediators of EE's benefits in AD is not well understood.

Purpose of the Study:

• To investigate the impact of EE on cognitive performance in APP23 transgenic mice, an Alzheimer's disease model.
• To assess the influence of EE on brain amyloid-beta (Aβ) burden and related molecular pathways.
• To explore the involvement of sirtuins (SIRTs) in mediating the effects of EE.

Main Methods:

• APP23 transgenic mice and wild-type littermates were housed in standard or enriched environments.
• Cognitive function was evaluated using the Morris Water Maze (MWM) and visual novel Object Recognition Test (vORT).
• Brain tissue was analyzed for Aβ levels, Aβ-degrading enzymes, and sirtuin (SIRT1-7) mRNA and protein expression.

Main Results:

• Environmental enrichment (EE) significantly improved cognitive performance in APP23 mice compared to standard housing.
• EE attenuated long-term Aβ deposition in the brains of aged APP23 mice.
• EE did not alter Aβ processing, Aβ oligomer levels, or sirtuin expression but increased brain-derived neurotrophic factor.

Conclusions:

• Environmental enrichment (EE) confers cognitive benefits and reduces long-term Aβ accumulation in an Alzheimer's disease mouse model.
• The beneficial effects of EE on cognition and Aβ burden may occur independently of sirtuin modulation.
• EE represents a viable strategy to mitigate cognitive decline and pathological hallmarks in Alzheimer's disease.