Background:Mitochondrial dysfunction plays a critical role in the pathogenesis of Alzheimer’s disease(AD).Resveratrol is a promising compound for the treatment of various neurodegenerative diseases,including AD.Aims:...Background:Mitochondrial dysfunction plays a critical role in the pathogenesis of Alzheimer’s disease(AD).Resveratrol is a promising compound for the treatment of various neurodegenerative diseases,including AD.Aims:To investigate mitochondrial damage and the effects of resveratrol on inflammation,cognitive function,and mitochondrial quality control in APP/PS1 mice.Methods:Comparative analysis of mitochondrial DNA(mtDNA)damage was conducted between 10-month-old APP/PS1 mice and age-matched C57BL/6 mice.Assessments included measurement of amyloid-βlevels,inflammatory markers,swimming distance in the Morris water maze,and gut microbiome composition.Resveratrol’s effects on cytokine expression,mtDNA levels in plasma,and activation of Nuclear factor erythroid 2-related factor 2/Antioxidant response element(Nrf2/ARE)and phosphoinositide 3-kinase/protein kinase B(also known as Akt)/mechanistic target of rapamycin complex 1(PI3K/Akt/mTORC1)signaling pathways were also evaluated.Results:APP/PS1 mice exhibited significantly increased mtDNA damage in the prefrontal cortex,midbrain,and cerebellum,alongside higher amyloid-βlevels and inflammatory markers.Resveratrol treatment led to reduced expression of pro-inflammatory cytokines,a decrease in Proteobacteria levels,and lower cell-free mtDNA in plasma.Partial improvement in long-term spatial memory was observed in APP/PS1 mice following resveratrol treatment,likely due to its anti-inflammatory properties.Activation of the Nrf2/ARE signaling pathway and markers of PI3K/Akt/mTORC1 axis activation were noted,with the latter regulating long-term potentiation.Conclusion:Resveratrol demonstrates potential in mitigating inflammation and improving mitochondrial quality control in APP/PS1 mice,but it does not reduce amyloid-βlevels,highlighting the complexity of AD pathology and the need for further research.展开更多
基金supported by the Russian science foundation(grant#22-74-00115 to A.P.G.).
文摘Background:Mitochondrial dysfunction plays a critical role in the pathogenesis of Alzheimer’s disease(AD).Resveratrol is a promising compound for the treatment of various neurodegenerative diseases,including AD.Aims:To investigate mitochondrial damage and the effects of resveratrol on inflammation,cognitive function,and mitochondrial quality control in APP/PS1 mice.Methods:Comparative analysis of mitochondrial DNA(mtDNA)damage was conducted between 10-month-old APP/PS1 mice and age-matched C57BL/6 mice.Assessments included measurement of amyloid-βlevels,inflammatory markers,swimming distance in the Morris water maze,and gut microbiome composition.Resveratrol’s effects on cytokine expression,mtDNA levels in plasma,and activation of Nuclear factor erythroid 2-related factor 2/Antioxidant response element(Nrf2/ARE)and phosphoinositide 3-kinase/protein kinase B(also known as Akt)/mechanistic target of rapamycin complex 1(PI3K/Akt/mTORC1)signaling pathways were also evaluated.Results:APP/PS1 mice exhibited significantly increased mtDNA damage in the prefrontal cortex,midbrain,and cerebellum,alongside higher amyloid-βlevels and inflammatory markers.Resveratrol treatment led to reduced expression of pro-inflammatory cytokines,a decrease in Proteobacteria levels,and lower cell-free mtDNA in plasma.Partial improvement in long-term spatial memory was observed in APP/PS1 mice following resveratrol treatment,likely due to its anti-inflammatory properties.Activation of the Nrf2/ARE signaling pathway and markers of PI3K/Akt/mTORC1 axis activation were noted,with the latter regulating long-term potentiation.Conclusion:Resveratrol demonstrates potential in mitigating inflammation and improving mitochondrial quality control in APP/PS1 mice,but it does not reduce amyloid-βlevels,highlighting the complexity of AD pathology and the need for further research.
