Electroacupuncture preconditioning at acupoint Baihui(GV20) can reduce focal cerebral ischemia/reperfusion injury. However, the precise protective mechanism remains unknown. Mitochondrial fission mediated by dynamin-r...Electroacupuncture preconditioning at acupoint Baihui(GV20) can reduce focal cerebral ischemia/reperfusion injury. However, the precise protective mechanism remains unknown. Mitochondrial fission mediated by dynamin-related protein 1(Drp1) can trigger neuronal apoptosis following cerebral ischemia/reperfusion injury. Herein, we examined the hypothesis that electroacupuncture pretreatment can regulate Drp1, and thus inhibit mitochondrial fission to provide cerebral protection. Rat models of focal cerebral ischemia/reperfusion injury were established by middle cerebral artery occlusion at 24 hours after 5 consecutive days of preconditioning with electroacupuncture at GV20(depth 2 mm, intensity 1 m A, frequency 2/15 Hz, for 30 minutes, once a day). Neurological function was assessed using the Longa neurological deficit score. Pathological changes in the ischemic penumbra on the injury side were assessed by hematoxylin-eosin staining. Cellular apoptosis in the ischemic penumbra on the injury side was assessed by terminal deoxyribonucleotidyl transferase-mediated d UTP-digoxigenin nick end labeling staining. Mitochondrial ultrastructure in the ischemic penumbra on the injury side was assessed by transmission electron microscopy. Drp1 and cytochrome c expression in the ischemic penumbra on the injury side were assessed by western blot assay. Results showed that electroacupuncture preconditioning decreased expression of total and mitochondrial Drp1, decreased expression of total and cytosolic cytochrome c, maintained mitochondrial morphology and reduced the proportion of apoptotic cells in the ischemic penumbra on the injury side, with associated improvements in neurological function. These data suggest that electroacupuncture preconditioning-induced neuronal protection involves inhibition of the expression and translocation of Drp1.展开更多
Background:Accumulating reports have suggested that α-synuclein is involved in the pathogenesis of Alzheimer's disease(AD).As the cerebrospinal fluid(CSF)α-synuclein has been suggested as a potential biomarker o...Background:Accumulating reports have suggested that α-synuclein is involved in the pathogenesis of Alzheimer's disease(AD).As the cerebrospinal fluid(CSF)α-synuclein has been suggested as a potential biomarker of AD,this study was set out to test whether CSF α-synuclein is associated with other AD biomarkers and could predict neurodegeneration and clinical progression in non-demented elders.Methods:The associations between CSF a-synuclein and other AD biomarkers were investigated at baseline in non-demented Chinese elders.The predictive values of CSF a-synuclein for longitudinal neuroimaging change and the conversion risk of non-demented elders were assessed using linear mixed effects models and multivariate Cox proportional hazard models,respectively,in the Alzheimer's disease Neuroimaging Initiative(ADNI)database.Results:The CSF α-synuclein levels correlated with AD-specific biomarkers,CSF total tau and phosphorylated tau levels,in 651 Chinese Han participants(training set).These positive correlations were replicated in the ADNI database(validation set).Using a longitudinal cohort from ADNI,the CSF α-synuclein concentrations were found to increase with disease severity.The CSF α-synuclein had high diagnostic accuracy for AD based on the"ATN"(amyloid,tau,neurodegeneration)system(A+T+versus A-T-control)(area under the receiver operating characteristic curve,0.84).Moreover,CSF α-synuclein predicted longitudinal hippocampus atrophy and conversion from MCI to AD dementia.Conclusions:CSF α-synuclein is associated with CSF tau levels and could predict neurodegeneration and clinical progression in non-demented elders.This finding indicates that CSF α-synuclein is a potentially useful early biomarker for AD.展开更多
基金supported by the Natural Science Foundation of Shandong Province of China,No.ZR2015HM023a grant from the Science and Technology Plan Project of Shinan District of Qingdao City of China,No.2016-3-029-YY
文摘Electroacupuncture preconditioning at acupoint Baihui(GV20) can reduce focal cerebral ischemia/reperfusion injury. However, the precise protective mechanism remains unknown. Mitochondrial fission mediated by dynamin-related protein 1(Drp1) can trigger neuronal apoptosis following cerebral ischemia/reperfusion injury. Herein, we examined the hypothesis that electroacupuncture pretreatment can regulate Drp1, and thus inhibit mitochondrial fission to provide cerebral protection. Rat models of focal cerebral ischemia/reperfusion injury were established by middle cerebral artery occlusion at 24 hours after 5 consecutive days of preconditioning with electroacupuncture at GV20(depth 2 mm, intensity 1 m A, frequency 2/15 Hz, for 30 minutes, once a day). Neurological function was assessed using the Longa neurological deficit score. Pathological changes in the ischemic penumbra on the injury side were assessed by hematoxylin-eosin staining. Cellular apoptosis in the ischemic penumbra on the injury side was assessed by terminal deoxyribonucleotidyl transferase-mediated d UTP-digoxigenin nick end labeling staining. Mitochondrial ultrastructure in the ischemic penumbra on the injury side was assessed by transmission electron microscopy. Drp1 and cytochrome c expression in the ischemic penumbra on the injury side were assessed by western blot assay. Results showed that electroacupuncture preconditioning decreased expression of total and mitochondrial Drp1, decreased expression of total and cytosolic cytochrome c, maintained mitochondrial morphology and reduced the proportion of apoptotic cells in the ischemic penumbra on the injury side, with associated improvements in neurological function. These data suggest that electroacupuncture preconditioning-induced neuronal protection involves inhibition of the expression and translocation of Drp1.
基金This study was supported by grants from the National Natural Science Foundation of China(91849126)the National Key R&D Program of China(2018YFC1314700)+2 种基金Shanghai Municipal Science and Technology Major Project(No.2018SHZDZX01)ZJLab,Shanghai Center for Brain Science and Brain-Inspired Technology,Tianqiao and Chrissy Chen Institute,and the State Key Laboratory of Neurobiology and Frontiers Center for Brain Science of Ministry of Education,Fudan University.Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative(ADNI)(National Institutes of Health Grant U01 AG024904)DOD ADNI(Department of Defense award number W81XWH-12-2-0012).
文摘Background:Accumulating reports have suggested that α-synuclein is involved in the pathogenesis of Alzheimer's disease(AD).As the cerebrospinal fluid(CSF)α-synuclein has been suggested as a potential biomarker of AD,this study was set out to test whether CSF α-synuclein is associated with other AD biomarkers and could predict neurodegeneration and clinical progression in non-demented elders.Methods:The associations between CSF a-synuclein and other AD biomarkers were investigated at baseline in non-demented Chinese elders.The predictive values of CSF a-synuclein for longitudinal neuroimaging change and the conversion risk of non-demented elders were assessed using linear mixed effects models and multivariate Cox proportional hazard models,respectively,in the Alzheimer's disease Neuroimaging Initiative(ADNI)database.Results:The CSF α-synuclein levels correlated with AD-specific biomarkers,CSF total tau and phosphorylated tau levels,in 651 Chinese Han participants(training set).These positive correlations were replicated in the ADNI database(validation set).Using a longitudinal cohort from ADNI,the CSF α-synuclein concentrations were found to increase with disease severity.The CSF α-synuclein had high diagnostic accuracy for AD based on the"ATN"(amyloid,tau,neurodegeneration)system(A+T+versus A-T-control)(area under the receiver operating characteristic curve,0.84).Moreover,CSF α-synuclein predicted longitudinal hippocampus atrophy and conversion from MCI to AD dementia.Conclusions:CSF α-synuclein is associated with CSF tau levels and could predict neurodegeneration and clinical progression in non-demented elders.This finding indicates that CSF α-synuclein is a potentially useful early biomarker for AD.
