Cognitive impairment is the main clinical manifestation of Alzheimer's disease(AD),and amyloid-β(AB)deposition and senile plaques are the characteristic neuropathological hallmarks in AD brains.This study aimed t...Cognitive impairment is the main clinical manifestation of Alzheimer's disease(AD),and amyloid-β(AB)deposition and senile plaques are the characteristic neuropathological hallmarks in AD brains.This study aimed to explore the effect and mechanism of tetrahydroxy stilbene glucoside(TSG)on cognitive function in APP/PS 1 mice during long-term administration.Here,we treated APP/PS1 model mice of AD with different doses of TSG(50 mg/kg and 100 mg/kg)for 5 to 17 months by gavage,and we further observed whether TSG could ameliorate the cognitive decline in APP/PS1 mice using behavioral tests,and investigated the possible mechanisms by immunohistochemistry and Western blotting.Our results showed that TSG treatment rescued the spatial and non-spatial learning and memory impairments of APP/PS1 mice at Morris water maze test and novel object recognition test.Furthermore,Aβ40/42 deposition in the cortex and hippocampus of APP/PS1 mice treated with TSG was significantly reduced compared to the wild type mice using the immunohistochemical technique.Finally,Western blotting showed that TSG primarily decreased the APP expression to avoid the Aβplaque deposition in the cortex and hippocampus of mice.These results reveal the beneficial effects of TSG in APP/PSI-AD mice,which may be associated with the reduction of Aβdeposits in the brain.展开更多
OBJECTIVE To investigate the effect of LW-AFC,a new formula of the main active components extracted fromLiuwei Dihuang decoction,on treatment of Alzheimer disease(AD) in mouse models.METHODS After treatment LW-AFC,mic...OBJECTIVE To investigate the effect of LW-AFC,a new formula of the main active components extracted fromLiuwei Dihuang decoction,on treatment of Alzheimer disease(AD) in mouse models.METHODS After treatment LW-AFC,mice were cognitively evaluated in behavioral experiments.Neuron loss,amyloid-β(Αβ) deposition,and Αβ level were analyzed using Nissl staining,immunofluorescence,and an Alpha LISA assay,respectively.Multiplex bead analysis,a radioimmunoassay,immunochemiluminometry,and an ELISA were used to measure cytokine and hormone levels.Lymphocyte subsets were detected using flow cytometry.RESULTS LW-AFC ameliorated the cognitive impairment observed in APP/PS1 mice,including the impairment of object recognition memory,spatial learning and memory,and active and passive avoidance.In addition,LW-AFC alleviated the neuron loss in the hippocampus,suppressed Αβ deposition in the brain,and reduced the concentration of Aβ1-42 in the hippocampus and plasma of APP/PS1 mice.LW-AFC treatment also significantly decreased the secretion of corticotropin-releasing hormone and gonadotropin-releasing hormone in the hypothalamus,and adrenocorticotropic hormone,luteinizing hormone,and follicle-stimulating hormone in the pituitary.Moreover,LW-AFC increased CD8+CD28+T cells,and reduced CD4^+CD25^+Foxp3^+T cells in the spleen lymphocytes,down-regulated interleukin(IL)-1β,IL-2,IL-6,IL-23,granulocyte-macrophage colony stimulating factor,and tumor necrosis factor-α and-β,and up-regulated IL-4 and granulocyte colony stimulating factor in the plasma of APP/PS1 mice.CONCLUSION LW-AFC ameliorated the behavioral and pathological deterioration of APP/PS1 transgenic micevia the restoration of the NIM network to a greater extent than either memantineor donepezil,which supports the use of LW-AFC as a potential agent for AD therapy.展开更多
目的研究二价金属离子转运体1(divalent metal transporter 1,DMT1)在APP/PS1转基因小鼠大脑皮层内的定位分布,探讨DMT1异常表达影响脑铁代谢平衡从而参与AD发病的可能机制。方法应用免疫组织化学方法观察DMT1在9月龄APPsw/PS1小鼠大脑...目的研究二价金属离子转运体1(divalent metal transporter 1,DMT1)在APP/PS1转基因小鼠大脑皮层内的定位分布,探讨DMT1异常表达影响脑铁代谢平衡从而参与AD发病的可能机制。方法应用免疫组织化学方法观察DMT1在9月龄APPsw/PS1小鼠大脑皮层的阳性分布;应用免疫荧光双标技术和共聚焦激光扫描显微镜观察DMT1蛋白和β淀粉样蛋白(β-amyloid peptide,Aβ)在APP/PS1转基因小鼠大脑皮层老年斑内的一致性分布和位置关系。结果APP/PS1转基因小鼠大脑皮层老年斑内均有DMT1阳性表达;DMT1和Aβ免疫双标发现DMT1免疫阳性产物与Aβ共存于老年斑,二者分布具有一致性。结论DMT1在APP/PS1转基因小鼠大脑皮层老年斑内大量表达,其分布与Aβ具有一致性,提示DMT1可能参与AD脑内Aβ沉积和老年斑形成。展开更多
基金supported by grants from the National Natural Science Foundation of China(No.81803537)the"Major New Drug Creation"of Major Science and Technology Project(No.2015ZX09101-016)+1 种基金Capital Science and Technology Leading Talent Training Project(No.Z191100006119017)Beijing Hospitals Authority Ascent Plan(No.DFL20190803)。
文摘Cognitive impairment is the main clinical manifestation of Alzheimer's disease(AD),and amyloid-β(AB)deposition and senile plaques are the characteristic neuropathological hallmarks in AD brains.This study aimed to explore the effect and mechanism of tetrahydroxy stilbene glucoside(TSG)on cognitive function in APP/PS 1 mice during long-term administration.Here,we treated APP/PS1 model mice of AD with different doses of TSG(50 mg/kg and 100 mg/kg)for 5 to 17 months by gavage,and we further observed whether TSG could ameliorate the cognitive decline in APP/PS1 mice using behavioral tests,and investigated the possible mechanisms by immunohistochemistry and Western blotting.Our results showed that TSG treatment rescued the spatial and non-spatial learning and memory impairments of APP/PS1 mice at Morris water maze test and novel object recognition test.Furthermore,Aβ40/42 deposition in the cortex and hippocampus of APP/PS1 mice treated with TSG was significantly reduced compared to the wild type mice using the immunohistochemical technique.Finally,Western blotting showed that TSG primarily decreased the APP expression to avoid the Aβplaque deposition in the cortex and hippocampus of mice.These results reveal the beneficial effects of TSG in APP/PSI-AD mice,which may be associated with the reduction of Aβdeposits in the brain.
基金supported by National Science and Technology Major Projects Initiative(2013ZX09508104)National Natural Science Foundation of China(81473191)
文摘OBJECTIVE To investigate the effect of LW-AFC,a new formula of the main active components extracted fromLiuwei Dihuang decoction,on treatment of Alzheimer disease(AD) in mouse models.METHODS After treatment LW-AFC,mice were cognitively evaluated in behavioral experiments.Neuron loss,amyloid-β(Αβ) deposition,and Αβ level were analyzed using Nissl staining,immunofluorescence,and an Alpha LISA assay,respectively.Multiplex bead analysis,a radioimmunoassay,immunochemiluminometry,and an ELISA were used to measure cytokine and hormone levels.Lymphocyte subsets were detected using flow cytometry.RESULTS LW-AFC ameliorated the cognitive impairment observed in APP/PS1 mice,including the impairment of object recognition memory,spatial learning and memory,and active and passive avoidance.In addition,LW-AFC alleviated the neuron loss in the hippocampus,suppressed Αβ deposition in the brain,and reduced the concentration of Aβ1-42 in the hippocampus and plasma of APP/PS1 mice.LW-AFC treatment also significantly decreased the secretion of corticotropin-releasing hormone and gonadotropin-releasing hormone in the hypothalamus,and adrenocorticotropic hormone,luteinizing hormone,and follicle-stimulating hormone in the pituitary.Moreover,LW-AFC increased CD8+CD28+T cells,and reduced CD4^+CD25^+Foxp3^+T cells in the spleen lymphocytes,down-regulated interleukin(IL)-1β,IL-2,IL-6,IL-23,granulocyte-macrophage colony stimulating factor,and tumor necrosis factor-α and-β,and up-regulated IL-4 and granulocyte colony stimulating factor in the plasma of APP/PS1 mice.CONCLUSION LW-AFC ameliorated the behavioral and pathological deterioration of APP/PS1 transgenic micevia the restoration of the NIM network to a greater extent than either memantineor donepezil,which supports the use of LW-AFC as a potential agent for AD therapy.
文摘目的研究二价金属离子转运体1(divalent metal transporter 1,DMT1)在APP/PS1转基因小鼠大脑皮层内的定位分布,探讨DMT1异常表达影响脑铁代谢平衡从而参与AD发病的可能机制。方法应用免疫组织化学方法观察DMT1在9月龄APPsw/PS1小鼠大脑皮层的阳性分布;应用免疫荧光双标技术和共聚焦激光扫描显微镜观察DMT1蛋白和β淀粉样蛋白(β-amyloid peptide,Aβ)在APP/PS1转基因小鼠大脑皮层老年斑内的一致性分布和位置关系。结果APP/PS1转基因小鼠大脑皮层老年斑内均有DMT1阳性表达;DMT1和Aβ免疫双标发现DMT1免疫阳性产物与Aβ共存于老年斑,二者分布具有一致性。结论DMT1在APP/PS1转基因小鼠大脑皮层老年斑内大量表达,其分布与Aβ具有一致性,提示DMT1可能参与AD脑内Aβ沉积和老年斑形成。
