In this study,we examined 3-month-old female mice from the senescence-accelerated prone mouse 8 strain and age-matched homologous normal aging female mice from the senescence accelerated-resistant mouse 1 strain.Mice ...In this study,we examined 3-month-old female mice from the senescence-accelerated prone mouse 8 strain and age-matched homologous normal aging female mice from the senescence accelerated-resistant mouse 1 strain.Mice from each strain were housed in an enriched environment（including a platform,running wheels,tunnel,and some toys）or a standard environment for 3 months.The mice housed in the enriched environment exhibited shorter escape latencies and a greater percentage of time in the target quadrant in the Morris water maze test,and they exhibited reduced errors and longer latencies in step-down avoidance experiments compared with mice housed in the standard environment.Correspondently,brain-derived neurotrophic factor mRNA and protein ex- pression in the hippocampus was significantly higher in mice housed in the enriched environment compared with those housed in the standard environment,and the level of hippocampal brain-derived neurotrophic factor protein was positively correlated with the learning and memory abilities of mice from the senescence-accelerated prone mouse 8 strain.These results suggest that an enriched environment improved cognitive performance in mice form the senescence-accelerated prone mouse 8 strain by increasing brain-derived neurotrophic factor expression in the hippocampus.展开更多
OBJECTIVE To investigate the effects of LW-AFC,a new formula derived fromLiuwei Dihuang decoction,on gut microbiota and the behavior of learning and memory of SAMP8 mice,a mouse model of Alzheimer Disease(AD),and iden...OBJECTIVE To investigate the effects of LW-AFC,a new formula derived fromLiuwei Dihuang decoction,on gut microbiota and the behavior of learning and memory of SAMP8 mice,a mouse model of Alzheimer Disease(AD),and identify the specific intestinal microbiota correlating with cognitive ability.METHODS Morris-water maze test,novel object recognition test and shuttle-box test were conducted to observe the ability of learning and memory.16S rRNA amplicon sequencing(Illumina,San Diego,CA,USA)was employed to investigate gut microbiota.RESULTS The treatment of LW-AFC improved cognitive impairments of SAMP8 mice,including spatial learning and memory ability,active avoidance response,and object recognition memory capability.Our data indicated that there were significantly 8 increased and 12 decreased operational taxonomic units(OTUs)in the gut microbiota of SAMP8 mice compared with senescence accelerated mouse resistant 1(SAMR1) strains,the control of SAMP8 mice.The treatment of LW-AFC altered 22(16 increased and 6 decreased)OTUs in SAMP8 mice and among them,15 OTUs could be reversed by LW-AFC treatment resulting in a microbial composition similar to that of SAMR1 mice.We further showed that there were7(3 negative and 4 positive correlation)OTUs significantly correlated with all the three types of cognitive abilities,at the order level,including Bacteroidales,Clostridiales,Desulfovibrionales,CW040,and two unclassified orders.LW-AFC had influences on bacterial taxa correlated with the abilities of learning and memory in SAMP8 mice and restored them to SAMR1 mice.CONCLUSION The effects of LW-AFC on improving cognitive impairments of SAMP8 mice might be via modulating intestinal microbiome and LW-AFC could be used as a potential anti-AD agent.展开更多
Objective： To investigate the preventive treatment effects of electroacupuncture（EA） on cognitive changes and brain damage in senescence-accelerated mouse prone 8（SAMP8） mice. Methods： The 5-month-old male SAMP8...Objective： To investigate the preventive treatment effects of electroacupuncture（EA） on cognitive changes and brain damage in senescence-accelerated mouse prone 8（SAMP8） mice. Methods： The 5-month-old male SAMP8 and age-matched homologous normal aging mice（SAMR1） were adopted in this study. EA stimulation at Baihui（GV 20） and Yintang（EX-HN 3） was performed every other day for 12 weeks, 4 weeks as a course. Morris water maze test and Nissl-stained with cresyl violet were used for cognitive impairments evaluation and brain morphometric analysis. Amyloid-β（Aβ） expression in hippocampus and parietal cortex was detected by immunohistochemistry, and apoptosis was observed by TUNEL staining. Results： After 3 courses of EA preventive treatment, the escape latencies of 8-month-old SAMP8 mice in EA group were significantly shortened than those of un-pretreated SAMP8 mice. Compared with SAMR1 mice, extensive neuronal changes were visualized in the CA1 area of hippocampus in SAMP8 mice, while these pathological changes and attenuate cell loss in hippocampal CA1 area of SAMP8 mice markedly reduced after EA preventive treatment. Furthermore, Aβ expression in hippocampus and parietal cortex of SAMP8 mice decreased significantly after EA treatment, and neuronal apoptosis decreased as well. Conclusion： EA preventive treatment at GV 20 and EX-HN 3 might improve cognitive deficits and neuropathological changes in SAMP8 mice, which might be, at least in part, due to the effects of reducing brain neuronal damage, decreasing neuronal apoptosis and inhibiting Aβ-containing aggregates.展开更多
Acupuncture can improve the cognitive state of Alzheimer＇s disease, but its mechanism is not clear. Dendritic atrophy and synaptic loss in Alzheimer＇s disease brain are positively correlated with cognitive damage. T...Acupuncture can improve the cognitive state of Alzheimer＇s disease, but its mechanism is not clear. Dendritic atrophy and synaptic loss in Alzheimer＇s disease brain are positively correlated with cognitive damage. Therefore, we speculated that the effect of acupuncture on improving cognitive function may be associated with reduced dendritic damage in the brain. Acupuncture at Qihai（CV6）, Zhongwan（CV12）, Danzhong（CV17）, bilateral Zusanli（ST36）, and bilateral Xuehai（SP10） acupoints was performed once a day（1-day rest after 6-day treatment） for 14 consecutive days. Senescence-accelerated mouse prone 8（SAMP8） mice without acupuncture and senescence-accelerated mouse resistant 1（SAMR1） mice were used as normal controls. After 14 days of treatment, spatial learning and memory ability of mice was assessed in each group using the Morris water maze. Dendritic changes of pyramidal cells in the hippocampal CA1 region were analyzed by quantitative Golgi staining. Our results showed that acupuncture shortened escape latency and lengthened retention time of the former platform quadrant in SAMP8 mice. Further, SAMP8 mice exhibited a significant increase in the number of apical and basal dendritic branches and total length of apical and basal dendrites after acupuncture. These results suggest that acupuncture improves spatial learning and memory ability of middle-aged SAMP8 mice by ameliorating dendritic structure.Acupuncture can improve the cognitive state of Alzheimer＇s disease, but its mechanism is not clear. Dendritic atrophy and synaptic loss in Alzheimer＇s disease brain are positively correlated with cognitive damage. Therefore, we speculated that the effect of acupuncture on im- proving cognitive function may be associated with reduced dendritic damage in the brain. Acupuncture at Qihai （CV6）, Zhongwan （CV 12）, Danzhong （CV17）, bilateral Zusanli （ST36）, and bilateral Xuehai （SP10） acupoints was performed once a day （1-day rest after 6-day treat- ment） for 14 consecutive days. Senescence-accelerated mouse prone 8 （SAMP8） mice without acupuncture and senescence-accelerated mouse resistant 1 （SAMR1） mice were used as normal controls. After 14 days of treatment, spatial learning and memory ability of mice was assessed in each group using the Morris water maze. Dendritic changes of pyramidal cells in the hippocampal CA1 region were analyzed by quantitative Golgi staining. Our results showed that acupuncture shortened escape latency and lengthened retention time of the former platform quadrant in SAMP8 mice. Further, SAMP8 mice exhibited a significant increase in the number of apical and basal dendritic branches and total length of apical and basal dendrites after acupuncture. These results suggest that acupuncture improves spatial learning and memory ability of middle-aged SAMP8 mice by ameliorating dendritic structure.展开更多
An enriched environment protects dopaminergic neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine（MPTP）-induced neuronal injury, but the underlying mechanism for this is not clear. Growth associated protein-43...An enriched environment protects dopaminergic neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine（MPTP）-induced neuronal injury, but the underlying mechanism for this is not clear. Growth associated protein-43（GAP-43） is closely associated with neurite outgrowth and axon regeneration during neural development. We speculate that an enriched environment can reduce damage to dopaminergic neurons by affecting the expression of GAP-43. This study is designed to test this hypothesis. Three-month-old female senescence-accelerated mouse prone 8（SAMP8） mice were housed for 3 months in an enriched environment or a standard environment. These mice were then subcutaneously injected in the abdomen with 14 mg/kg MPTP four times at 2-hour intervals. Morris water maze testing demonstrated that learning and memory abilities were better in the enriched environment group than in the standard environment group. Reverse-transcription polymerase chain reaction, immunohistochemistry and western blot assays showed that m RNA and protein levels of GAP-43 in the substantia nigra were higher after MPTP application in the enriched environment group compared with the standard environment group. These findings indicate that an enriched environment can increase GAP-43 expression in SAMP8 mice. The upregulation of GAP-43 may be a mechanism by which an enriched environment protects against MPTP-induced neuronal damage.展开更多
基金supported by the Program of Health Department of Hebei Province,No.20090338the Natural Science Foundation of Hebei Province,No.C2009001242Funding Project for Introduced Abroad Study Personnel of Hebei Province
文摘In this study,we examined 3-month-old female mice from the senescence-accelerated prone mouse 8 strain and age-matched homologous normal aging female mice from the senescence accelerated-resistant mouse 1 strain.Mice from each strain were housed in an enriched environment（including a platform,running wheels,tunnel,and some toys）or a standard environment for 3 months.The mice housed in the enriched environment exhibited shorter escape latencies and a greater percentage of time in the target quadrant in the Morris water maze test,and they exhibited reduced errors and longer latencies in step-down avoidance experiments compared with mice housed in the standard environment.Correspondently,brain-derived neurotrophic factor mRNA and protein ex- pression in the hippocampus was significantly higher in mice housed in the enriched environment compared with those housed in the standard environment,and the level of hippocampal brain-derived neurotrophic factor protein was positively correlated with the learning and memory abilities of mice from the senescence-accelerated prone mouse 8 strain.These results suggest that an enriched environment improved cognitive performance in mice form the senescence-accelerated prone mouse 8 strain by increasing brain-derived neurotrophic factor expression in the hippocampus.
基金supported by National Science and Technology Major Project(2013ZX09508104,2012ZX09301003-002-001)
文摘OBJECTIVE To investigate the effects of LW-AFC,a new formula derived fromLiuwei Dihuang decoction,on gut microbiota and the behavior of learning and memory of SAMP8 mice,a mouse model of Alzheimer Disease(AD),and identify the specific intestinal microbiota correlating with cognitive ability.METHODS Morris-water maze test,novel object recognition test and shuttle-box test were conducted to observe the ability of learning and memory.16S rRNA amplicon sequencing(Illumina,San Diego,CA,USA)was employed to investigate gut microbiota.RESULTS The treatment of LW-AFC improved cognitive impairments of SAMP8 mice,including spatial learning and memory ability,active avoidance response,and object recognition memory capability.Our data indicated that there were significantly 8 increased and 12 decreased operational taxonomic units(OTUs)in the gut microbiota of SAMP8 mice compared with senescence accelerated mouse resistant 1(SAMR1) strains,the control of SAMP8 mice.The treatment of LW-AFC altered 22(16 increased and 6 decreased)OTUs in SAMP8 mice and among them,15 OTUs could be reversed by LW-AFC treatment resulting in a microbial composition similar to that of SAMR1 mice.We further showed that there were7(3 negative and 4 positive correlation)OTUs significantly correlated with all the three types of cognitive abilities,at the order level,including Bacteroidales,Clostridiales,Desulfovibrionales,CW040,and two unclassified orders.LW-AFC had influences on bacterial taxa correlated with the abilities of learning and memory in SAMP8 mice and restored them to SAMR1 mice.CONCLUSION The effects of LW-AFC on improving cognitive impairments of SAMP8 mice might be via modulating intestinal microbiome and LW-AFC could be used as a potential anti-AD agent.
基金Supported by the National Natureal Science Foundation of China(No.30701121)
文摘Objective： To investigate the preventive treatment effects of electroacupuncture（EA） on cognitive changes and brain damage in senescence-accelerated mouse prone 8（SAMP8） mice. Methods： The 5-month-old male SAMP8 and age-matched homologous normal aging mice（SAMR1） were adopted in this study. EA stimulation at Baihui（GV 20） and Yintang（EX-HN 3） was performed every other day for 12 weeks, 4 weeks as a course. Morris water maze test and Nissl-stained with cresyl violet were used for cognitive impairments evaluation and brain morphometric analysis. Amyloid-β（Aβ） expression in hippocampus and parietal cortex was detected by immunohistochemistry, and apoptosis was observed by TUNEL staining. Results： After 3 courses of EA preventive treatment, the escape latencies of 8-month-old SAMP8 mice in EA group were significantly shortened than those of un-pretreated SAMP8 mice. Compared with SAMR1 mice, extensive neuronal changes were visualized in the CA1 area of hippocampus in SAMP8 mice, while these pathological changes and attenuate cell loss in hippocampal CA1 area of SAMP8 mice markedly reduced after EA preventive treatment. Furthermore, Aβ expression in hippocampus and parietal cortex of SAMP8 mice decreased significantly after EA treatment, and neuronal apoptosis decreased as well. Conclusion： EA preventive treatment at GV 20 and EX-HN 3 might improve cognitive deficits and neuropathological changes in SAMP8 mice, which might be, at least in part, due to the effects of reducing brain neuronal damage, decreasing neuronal apoptosis and inhibiting Aβ-containing aggregates.
基金supported by the National Natural Science Foundation of China,No.81603686,81603684the High School Science and Technology Fund Planning Project of Tianjin of China,No.20120211+1 种基金the Natural Science Foundation of Tianjin of China(Key Program),No.15JCZDJC36700,16JCZDJC37500the Natural Science Foundation of Tianjin of China,No.17JCYBJC26200
文摘Acupuncture can improve the cognitive state of Alzheimer＇s disease, but its mechanism is not clear. Dendritic atrophy and synaptic loss in Alzheimer＇s disease brain are positively correlated with cognitive damage. Therefore, we speculated that the effect of acupuncture on improving cognitive function may be associated with reduced dendritic damage in the brain. Acupuncture at Qihai（CV6）, Zhongwan（CV12）, Danzhong（CV17）, bilateral Zusanli（ST36）, and bilateral Xuehai（SP10） acupoints was performed once a day（1-day rest after 6-day treatment） for 14 consecutive days. Senescence-accelerated mouse prone 8（SAMP8） mice without acupuncture and senescence-accelerated mouse resistant 1（SAMR1） mice were used as normal controls. After 14 days of treatment, spatial learning and memory ability of mice was assessed in each group using the Morris water maze. Dendritic changes of pyramidal cells in the hippocampal CA1 region were analyzed by quantitative Golgi staining. Our results showed that acupuncture shortened escape latency and lengthened retention time of the former platform quadrant in SAMP8 mice. Further, SAMP8 mice exhibited a significant increase in the number of apical and basal dendritic branches and total length of apical and basal dendrites after acupuncture. These results suggest that acupuncture improves spatial learning and memory ability of middle-aged SAMP8 mice by ameliorating dendritic structure.Acupuncture can improve the cognitive state of Alzheimer＇s disease, but its mechanism is not clear. Dendritic atrophy and synaptic loss in Alzheimer＇s disease brain are positively correlated with cognitive damage. Therefore, we speculated that the effect of acupuncture on im- proving cognitive function may be associated with reduced dendritic damage in the brain. Acupuncture at Qihai （CV6）, Zhongwan （CV 12）, Danzhong （CV17）, bilateral Zusanli （ST36）, and bilateral Xuehai （SP10） acupoints was performed once a day （1-day rest after 6-day treat- ment） for 14 consecutive days. Senescence-accelerated mouse prone 8 （SAMP8） mice without acupuncture and senescence-accelerated mouse resistant 1 （SAMR1） mice were used as normal controls. After 14 days of treatment, spatial learning and memory ability of mice was assessed in each group using the Morris water maze. Dendritic changes of pyramidal cells in the hippocampal CA1 region were analyzed by quantitative Golgi staining. Our results showed that acupuncture shortened escape latency and lengthened retention time of the former platform quadrant in SAMP8 mice. Further, SAMP8 mice exhibited a significant increase in the number of apical and basal dendritic branches and total length of apical and basal dendrites after acupuncture. These results suggest that acupuncture improves spatial learning and memory ability of middle-aged SAMP8 mice by ameliorating dendritic structure.
基金supported by a grant from the Health Department of Hebei Province of China,No.20120056,20140314the Funding Project for Introduced Abroad Study Personnel of Hebei Province of China,No.C2011003039
文摘An enriched environment protects dopaminergic neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine（MPTP）-induced neuronal injury, but the underlying mechanism for this is not clear. Growth associated protein-43（GAP-43） is closely associated with neurite outgrowth and axon regeneration during neural development. We speculate that an enriched environment can reduce damage to dopaminergic neurons by affecting the expression of GAP-43. This study is designed to test this hypothesis. Three-month-old female senescence-accelerated mouse prone 8（SAMP8） mice were housed for 3 months in an enriched environment or a standard environment. These mice were then subcutaneously injected in the abdomen with 14 mg/kg MPTP four times at 2-hour intervals. Morris water maze testing demonstrated that learning and memory abilities were better in the enriched environment group than in the standard environment group. Reverse-transcription polymerase chain reaction, immunohistochemistry and western blot assays showed that m RNA and protein levels of GAP-43 in the substantia nigra were higher after MPTP application in the enriched environment group compared with the standard environment group. These findings indicate that an enriched environment can increase GAP-43 expression in SAMP8 mice. The upregulation of GAP-43 may be a mechanism by which an enriched environment protects against MPTP-induced neuronal damage.
