Acute cerebral ischemia caused by stroke,traumatic brain injury(TBI),or systemic acute conditions such as hemorrhagic shock,cardiac arrest,or disseminated intravascular coagulation results in an energy crisis in local...Acute cerebral ischemia caused by stroke,traumatic brain injury(TBI),or systemic acute conditions such as hemorrhagic shock,cardiac arrest,or disseminated intravascular coagulation results in an energy crisis in local sites or the whole brain.The disruption of cerebral blood flow deprives the brain cells of oxygen and glucose,the essential substrates for adenosine triphosphate(ATP)synthesis.As a result,oxidative phosphorylation in the mitochondria fails,forcing cells to rely on anaerobic glycolysis(He et al.,2020).Although this compensatory mechanism maintains short-term energy production under hypoxic conditions,overall ATP production is significantly reduced.Neurons,which are highly susceptible to ischemic injury,deplete their ATP stores faster than glial cells(e.g.,astrocytes),which have some energy reserves.展开更多
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 24-75-10013(to NVA).
文摘Acute cerebral ischemia caused by stroke,traumatic brain injury(TBI),or systemic acute conditions such as hemorrhagic shock,cardiac arrest,or disseminated intravascular coagulation results in an energy crisis in local sites or the whole brain.The disruption of cerebral blood flow deprives the brain cells of oxygen and glucose,the essential substrates for adenosine triphosphate(ATP)synthesis.As a result,oxidative phosphorylation in the mitochondria fails,forcing cells to rely on anaerobic glycolysis(He et al.,2020).Although this compensatory mechanism maintains short-term energy production under hypoxic conditions,overall ATP production is significantly reduced.Neurons,which are highly susceptible to ischemic injury,deplete their ATP stores faster than glial cells(e.g.,astrocytes),which have some energy reserves.
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.
