Objective To investigate the relations between neuroapoptosis and the onset and development of Alzheimer’s disease （AD）, especially the role of NF-κB in the regulation of neuroapoptosis. Methods Caspase-3 and NF-...Objective To investigate the relations between neuroapoptosis and the onset and development of Alzheimer’s disease （AD）, especially the role of NF-κB in the regulation of neuroapoptosis. Methods Caspase-3 and NF-κB （p50） expressions in the CA3 region of the hippocampus in APPswe Tg2576 transgenic mice were studied from postnatal day 0-180, using Nissl staining, immunohistochemistry and RT-PCR methods. Results Both neuronal apoptosis and NF-κB activity decreased gradually with the increase of age in wild type and Tg2576 mice. However, the number of caspase-3-positive or NF- κB-positive pyramidal cells in Tg2576 mice was greater than that in age-matched wild type mice, with significant differences after postnatal day 14 （P 0.01 or P 0.05）. Linear regression analyses of caspase-3 and NF-κB expression demonstrated a correlation between neuroapoptosis and activity of NF-κB. Conclusion The process of neuroapoptosis is consistent with the onset and development of AD. Furthermore, the observed correlation between neuroapoptosis and NF-κB activity suggests a role of NF-κB in hippocampal neuroapoptosis.展开更多
Objective To investigate the mechanism of electroacupuncture （EA） in treating Alzheimer＇s disease （AD） from aspect of mitochondria. Methods Twelve 8-month old SAMP8 mice were randomly divided into a model group ...Objective To investigate the mechanism of electroacupuncture （EA） in treating Alzheimer＇s disease （AD） from aspect of mitochondria. Methods Twelve 8-month old SAMP8 mice were randomly divided into a model group （Group Mod, n=6） and an electroacupuncture group （Group EA, n=6）, and six 8-month old SAMR1 mice were selected as a control group （Group Cont）. Animals in Group EA was treated with EA at ＂Baihui＂ （百会 GV 20）, ＂Dazhui＂ （大椎 GV 14）, ＂Shenshu （肾俞 BL 23） and ＂Taixi＂ （太溪 KI 3） for 20 min, once daily with 20 days of treatments as a therapeutic course, lasting for 3 courses. Mice in the other two groups were fixed in the same way as those in Group EA at the same time without any treatment. After treatment, learning and memory abilities of the mice were measured by Morris water maze, activities of enzyme complex of hippocampal mitochondrial respiratory chain were measured by spectrophotometry, and levels of adenosine triphosphate （ATP） were detected by reverse phase high performance liquid chromatography （HPLC） method. Results Compared with Group Cont, the average escape latency in Group Mod was significantly prolonged, the residence time on the platform quadrant was shortened, the activities of enzyme complex Ⅰ, Ⅱ, Ⅲ and Ⅳ in hippocampal mitochondrial respiratory chain was decreased, and ATP contents was lessened in Group Mod. Compared with Group Mod, the average escape latency was significantly shortened, the residence time on the platform quadrant was lengthened, the activities of enzyme complex Ⅰ, Ⅱ, Ⅲ and Ⅳ in hippocampal mitochondria respiratory chain were significantly increased, and ATP contents were also increased in Group EA. Conclusion Electroacupuncture can elevate the activities of enzyme complex in hippocampal mitochondrial respiratory chain and ATP contents, and improve mitochondrial functions, which may be one of the underlying mechanisms of EA in treatment of AD.展开更多
Objective:To evaluate the prevention and treatment effects of acupuncture-moxibustion for Alzheimer disease(AD)based on various AD mouse models.Methods:Several representative types of mouse models were selected accord...Objective:To evaluate the prevention and treatment effects of acupuncture-moxibustion for Alzheimer disease(AD)based on various AD mouse models.Methods:Several representative types of mouse models were selected according to the pathophysiological causes of AD,including senescence accelerated mouse/prone(SAMP)mice,soluble amyloid-βprotein(Aβ)injection mice/rats,amyloid precursor protein(APP)transgenic mice,and APP/PS1 double transgenic mice.Through the observation of behavioral changes and analysis of core items,the possible mechanisms of acupuncture-moxibustion in preventing and treating AD were explored.Results:Acupuncture-moxibusiton therapy can improve AD mice's cognitive dysfunction;the major action mechanisms including increasing cerebral blood flow,improving the expressions of vital proteins in the hippocampus,preventing neuron cell apoptosis,promoting the clearance of Aβdeposition,activating autophagy pathway to reduce memory deficits and regulating the metabolisms of brain-derived neurotrophic factor,tyrosine kinase receptor B,N-acetylaspartate and glutamic acid.Conclusion:Although the optimal mouse model is not determined,it is sure that acupuncture-moxibustion therapy can improve cognitive function.A more suitable AD animal model should be duplicated in order to better explore the inherent action mechanism of acupuncture-moxibustion in preventing and treating AD.展开更多
OBJECTIVE： To study the chemical constituents of Zhizi （Fructus Gardeniae） and their antiamnesic ef- fect in a mouse model of Alzheimer＇s disease. METHODS： Ameliorating effects of the extracts, fractions and cons...OBJECTIVE： To study the chemical constituents of Zhizi （Fructus Gardeniae） and their antiamnesic ef- fect in a mouse model of Alzheimer＇s disease. METHODS： Ameliorating effects of the extracts, fractions and constituents on scopolamine-in- duced memory impairment in vivo using a passive avoidance task system and their inhibitory activi- ties on acetylcholinesterase （ACHE） in vitro were ex- amined. The isolation of components was per- formed by chromatographic techniques and their structures were identified on the basis of spectral analysis. RESULTS： Activity-guided fractionation of the total extracts resulted in the isolation of two glycosides, geniposide and cr0cin from the n-butanol fraction and genipin and crocetin from the ethylacetate fraction. Among the fractions tested, n-butanol fraction showed the strongest AChE inhibition （43.4% at a final dose of 0.03 mg/mL） and also ex- hibited outstanding efficacy （65.9% at a dose of2.50 mg/kg） in an experimental model of amnesia. Geniposide showed a 22.8% AChE inhibitory activi- ty and a potent ameliorating effect on scopol- amine-induced memory impairment in amnesic mice of 93.4% as compared to the control group. CONCLUSION： Geniposide, a main constituent of gardenia should be considered a candidate for fur- ther clinical study for the purpose of developing a cognition activator and its mechanism of action may be mediated, at least in part, by the acetylcho- line enhancing cholinergic nervous system.展开更多
Objective The double transgenic mouse model （APPswe/PSldE9） of Alzheimer＇s disease （AD） has been widely used in experimental studies. β-Amyloid （Aβ） peptide is excessively produced in AD mouse brain, which af...Objective The double transgenic mouse model （APPswe/PSldE9） of Alzheimer＇s disease （AD） has been widely used in experimental studies. β-Amyloid （Aβ） peptide is excessively produced in AD mouse brain, which affects synaptic function and the development of central nervous system. However, little has been reported on characterization of this model. The present study aimed to characterize this mouse AD model and its wild-type counterparts by biochemical and functional approaches. Methods Blood samples were collected from the transgenic and the wild-type mice, and radial arm water maze behavioral test was conducted at the ages of 6 and 12 months. The mice were sacrificed at 12-month age. One hemisphere of the brain was frozen-sectioned for immunohistochemistry and the other hemisphere was dissected into 7 regions. The levels ofAβ1-40, Aβ1-42 and 8-hydroxydeoxyguanosine （8-OHdG） in blood or/and brain samples were analyzed by ELISA. Secretase activities in brain regions were analyzed by in vitro assays. Results The pre-mature death rate of transgenic mice was approximately 35% before 6-month age, and high levels of Aβ1-40 and Aβ1-42 were detected in these dead mice brains with a ratio of 1 ： 1 0. The level of blood-borne Aβ at 6-month age was similar with that at 12-month age. Besides, Aβ1-40 level in the blood was significantly higher than Aβ1-42 level at the ages of 6 and 12 months （ratio 2.37：1）. In contrast, the level of Aβ1-42 in the brain （160.6 ng/mg protein） was higher than that of Aβ1-40 （74 ng/mg protein） （ratio 2.17：1）. In addition, the levels of Aβ1-40 and Aβ1-42 varied markedly among different brain regions. Aβ1-42 level was significantly higher than Aβ1-40 level in cerebellum, frontal and posterior cortex, and hippocampus. Secretase activity assays did not reveal major differences among different brain regions or between wild-type and transgenic mice, suggesting that the transgene PS1 did not lead to higher 7-secretase activity but was more efficient in producing Aβ1-42 peptides. 8-OHdG, the biomarker of DNA oxidative damage, showed a trend of increase in the blood of transgenic mice, but with no significant difference, as compared with the wild-type mice. Behavioral tests showed that transgenic mice had significant memory deficits at 6-month age compared to wild-type controls, and the deficits were exacerbated at 12-month age with more errors. Conclusion These results suggest that this mouse model mimics the early-onset human AD and may represent full-blown disease at as early as 6-month age for experimental studies.展开更多
基金supported by theNational Natural Science Foundation of China (No. 30670688,30771140)the Natural Science Foundation of Education De-partment of Henan Province (No. 2007180008)+1 种基金the Natural Science Key Program of Henan University (No. 2008YBGG048)the International Cooperation Program of Science andTechnique Department of Henan Province, China (No.094300510044)
文摘Objective To investigate the relations between neuroapoptosis and the onset and development of Alzheimer’s disease （AD）, especially the role of NF-κB in the regulation of neuroapoptosis. Methods Caspase-3 and NF-κB （p50） expressions in the CA3 region of the hippocampus in APPswe Tg2576 transgenic mice were studied from postnatal day 0-180, using Nissl staining, immunohistochemistry and RT-PCR methods. Results Both neuronal apoptosis and NF-κB activity decreased gradually with the increase of age in wild type and Tg2576 mice. However, the number of caspase-3-positive or NF- κB-positive pyramidal cells in Tg2576 mice was greater than that in age-matched wild type mice, with significant differences after postnatal day 14 （P 0.01 or P 0.05）. Linear regression analyses of caspase-3 and NF-κB expression demonstrated a correlation between neuroapoptosis and activity of NF-κB. Conclusion The process of neuroapoptosis is consistent with the onset and development of AD. Furthermore, the observed correlation between neuroapoptosis and NF-κB activity suggests a role of NF-κB in hippocampal neuroapoptosis.
基金Supported by National Natural Science Fund Project of China:81102625Henan Province Science Foundation for Youths:2010269
文摘Objective To investigate the mechanism of electroacupuncture （EA） in treating Alzheimer＇s disease （AD） from aspect of mitochondria. Methods Twelve 8-month old SAMP8 mice were randomly divided into a model group （Group Mod, n=6） and an electroacupuncture group （Group EA, n=6）, and six 8-month old SAMR1 mice were selected as a control group （Group Cont）. Animals in Group EA was treated with EA at ＂Baihui＂ （百会 GV 20）, ＂Dazhui＂ （大椎 GV 14）, ＂Shenshu （肾俞 BL 23） and ＂Taixi＂ （太溪 KI 3） for 20 min, once daily with 20 days of treatments as a therapeutic course, lasting for 3 courses. Mice in the other two groups were fixed in the same way as those in Group EA at the same time without any treatment. After treatment, learning and memory abilities of the mice were measured by Morris water maze, activities of enzyme complex of hippocampal mitochondrial respiratory chain were measured by spectrophotometry, and levels of adenosine triphosphate （ATP） were detected by reverse phase high performance liquid chromatography （HPLC） method. Results Compared with Group Cont, the average escape latency in Group Mod was significantly prolonged, the residence time on the platform quadrant was shortened, the activities of enzyme complex Ⅰ, Ⅱ, Ⅲ and Ⅳ in hippocampal mitochondrial respiratory chain was decreased, and ATP contents was lessened in Group Mod. Compared with Group Mod, the average escape latency was significantly shortened, the residence time on the platform quadrant was lengthened, the activities of enzyme complex Ⅰ, Ⅱ, Ⅲ and Ⅳ in hippocampal mitochondria respiratory chain were significantly increased, and ATP contents were also increased in Group EA. Conclusion Electroacupuncture can elevate the activities of enzyme complex in hippocampal mitochondrial respiratory chain and ATP contents, and improve mitochondrial functions, which may be one of the underlying mechanisms of EA in treatment of AD.
文摘Objective:To evaluate the prevention and treatment effects of acupuncture-moxibustion for Alzheimer disease(AD)based on various AD mouse models.Methods:Several representative types of mouse models were selected according to the pathophysiological causes of AD,including senescence accelerated mouse/prone(SAMP)mice,soluble amyloid-βprotein(Aβ)injection mice/rats,amyloid precursor protein(APP)transgenic mice,and APP/PS1 double transgenic mice.Through the observation of behavioral changes and analysis of core items,the possible mechanisms of acupuncture-moxibustion in preventing and treating AD were explored.Results:Acupuncture-moxibusiton therapy can improve AD mice's cognitive dysfunction;the major action mechanisms including increasing cerebral blood flow,improving the expressions of vital proteins in the hippocampus,preventing neuron cell apoptosis,promoting the clearance of Aβdeposition,activating autophagy pathway to reduce memory deficits and regulating the metabolisms of brain-derived neurotrophic factor,tyrosine kinase receptor B,N-acetylaspartate and glutamic acid.Conclusion:Although the optimal mouse model is not determined,it is sure that acupuncture-moxibustion therapy can improve cognitive function.A more suitable AD animal model should be duplicated in order to better explore the inherent action mechanism of acupuncture-moxibustion in preventing and treating AD.
基金Supported by the Ministry of Education,Science and Technology (MEST)Korea Institute for Advancement of Technology (KIAT) through the Human Resource Training Project for Regional Innovation
文摘OBJECTIVE： To study the chemical constituents of Zhizi （Fructus Gardeniae） and their antiamnesic ef- fect in a mouse model of Alzheimer＇s disease. METHODS： Ameliorating effects of the extracts, fractions and constituents on scopolamine-in- duced memory impairment in vivo using a passive avoidance task system and their inhibitory activi- ties on acetylcholinesterase （ACHE） in vitro were ex- amined. The isolation of components was per- formed by chromatographic techniques and their structures were identified on the basis of spectral analysis. RESULTS： Activity-guided fractionation of the total extracts resulted in the isolation of two glycosides, geniposide and cr0cin from the n-butanol fraction and genipin and crocetin from the ethylacetate fraction. Among the fractions tested, n-butanol fraction showed the strongest AChE inhibition （43.4% at a final dose of 0.03 mg/mL） and also ex- hibited outstanding efficacy （65.9% at a dose of2.50 mg/kg） in an experimental model of amnesia. Geniposide showed a 22.8% AChE inhibitory activi- ty and a potent ameliorating effect on scopol- amine-induced memory impairment in amnesic mice of 93.4% as compared to the control group. CONCLUSION： Geniposide, a main constituent of gardenia should be considered a candidate for fur- ther clinical study for the purpose of developing a cognition activator and its mechanism of action may be mediated, at least in part, by the acetylcho- line enhancing cholinergic nervous system.
基金supported by ApoPharma Inc.through a collaborative research project between NRC-IBS and ApoPharma Inc
文摘Objective The double transgenic mouse model （APPswe/PSldE9） of Alzheimer＇s disease （AD） has been widely used in experimental studies. β-Amyloid （Aβ） peptide is excessively produced in AD mouse brain, which affects synaptic function and the development of central nervous system. However, little has been reported on characterization of this model. The present study aimed to characterize this mouse AD model and its wild-type counterparts by biochemical and functional approaches. Methods Blood samples were collected from the transgenic and the wild-type mice, and radial arm water maze behavioral test was conducted at the ages of 6 and 12 months. The mice were sacrificed at 12-month age. One hemisphere of the brain was frozen-sectioned for immunohistochemistry and the other hemisphere was dissected into 7 regions. The levels ofAβ1-40, Aβ1-42 and 8-hydroxydeoxyguanosine （8-OHdG） in blood or/and brain samples were analyzed by ELISA. Secretase activities in brain regions were analyzed by in vitro assays. Results The pre-mature death rate of transgenic mice was approximately 35% before 6-month age, and high levels of Aβ1-40 and Aβ1-42 were detected in these dead mice brains with a ratio of 1 ： 1 0. The level of blood-borne Aβ at 6-month age was similar with that at 12-month age. Besides, Aβ1-40 level in the blood was significantly higher than Aβ1-42 level at the ages of 6 and 12 months （ratio 2.37：1）. In contrast, the level of Aβ1-42 in the brain （160.6 ng/mg protein） was higher than that of Aβ1-40 （74 ng/mg protein） （ratio 2.17：1）. In addition, the levels of Aβ1-40 and Aβ1-42 varied markedly among different brain regions. Aβ1-42 level was significantly higher than Aβ1-40 level in cerebellum, frontal and posterior cortex, and hippocampus. Secretase activity assays did not reveal major differences among different brain regions or between wild-type and transgenic mice, suggesting that the transgene PS1 did not lead to higher 7-secretase activity but was more efficient in producing Aβ1-42 peptides. 8-OHdG, the biomarker of DNA oxidative damage, showed a trend of increase in the blood of transgenic mice, but with no significant difference, as compared with the wild-type mice. Behavioral tests showed that transgenic mice had significant memory deficits at 6-month age compared to wild-type controls, and the deficits were exacerbated at 12-month age with more errors. Conclusion These results suggest that this mouse model mimics the early-onset human AD and may represent full-blown disease at as early as 6-month age for experimental studies.
