Impacto y mecanismos del ambiente enriquecido en la función cognitiva en ratones modelo de la enfermedad de Alzheimer

Objective: To investigate the effects and mechanisms of enriched environment(EE) on cognitive function in Alzheimer's disease (AD) model mice. Methods: Sixteen male 6-month-old APP/PS1 mice of SPF grade were randomly divided into standard environment group (AD group), and enriched environment group (ADEE group), with 8 mice in each group. Additionally, 16 C57BL/6J mice with matched body weight were selected as the control group and randomly divided into an enriched environment group (NCEE group) and a control group (NC group), with 8 mice in each group. The mice were adapted to the environment for 2 weeks, followed by 12 weeks of intervention. The Morris water maze test was used to assess learning, memory, and exploration abilities; Immunofluorescence staining and Western blot (WB) were performed to detect the levels of Aβ, Tau protein, silent information regulator 1 (SIRT1), and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α). Results: The Morris water maze test showed that the AD group had fewer platform crossings, fewer effective area crossings, shorter effective area dwell time, fewer target quadrant entries, and shorter target quadrant dwell time compared to the NC group (all P<0.05). In contrast, the ADEE group exhibited more effective area crossings, longer effective area dwell time, more target quadrant entries, and longer target quadrant dwell time compared to the AD group (all P<0.05). Immunofluorescence staining results revealed more Aβplaques and Tau protein positive cells in the AD group and ADEE group compared to the NC group and NCEE group (all P<0.01). After EE intervention, the ADEE group exhibited lower Aβ plaques and Tau protein positive cells than the AD group (all P<0.05). Immunofluorescence staining and WB both demonstrated that SIRT1 and PGC-1α expression in AD mice was lower than in NCEE and NC mice (all P<0.05). Following EE intervention, both the ADEE and NCEE groups showed higher SIRT1 and PGC-1α levels compared to the AD group and NC group (all P<0.05). Conclusion: EE may improve the pathological progression and cognitive impairment of AD by activating the SIRT1/PGC-1α signaling pathway.