OBJECTIVE To investigate the effects of imperatorin on the spatial learning memory impairment and neuroinflammation in model mice of Alzheimer disease(AD)induced by intracerebroventricular injection of Aβ1-42.METHODS...OBJECTIVE To investigate the effects of imperatorin on the spatial learning memory impairment and neuroinflammation in model mice of Alzheimer disease(AD)induced by intracerebroventricular injection of Aβ1-42.METHODS Mouse model of AD was established by injection of Aβ1-42 into the lateral ventricles.Im⁃peratorin(2.5 and 5.0 mg·kg-1,daily)was inject⁃ed by intraperitoneally 1 h after intracerebroven⁃tricular injection for 13 d.The effect of imperato⁃rin on the spatial learning and memory impair⁃ment was assessed by eight arm maze tests.The levels of cytokines TNF-α,IL-1β,IL-6,IL-18 and chemokines MCP-1 in mouse cortex and hip⁃pocampus were detected by ELISA.The protein expression of NF-κB P65,TLR4,MyD88,p-P38,p-ERK,and p-JNK were detected by Western blotting.RESULTS As compared with the AD model group,imperatorin treatment significantly attenuated Aβ1-42-induced spatial learning and memory impairment assessed by eight arm maze tests.In addition,imperatorin significantly reduced the levels of cytokines TNF-α,IL-1β,IL-6,IL-18 and chemokines MCP-1 in the cerebral cortex and hippocampus.Meanwhile,Western blotting results showed that imperatorin treat⁃ment significantly down-regulated the protein expression of NF-κB P65,TLR4,MyD88,p-P38,p-ERK,and p-JNK.CONCLUSION Imperatorin has neuroprotective effects in the Aβ1-42 induced AD model mice and its mechanism may be partially associated with the inhibition of inflam⁃matory response in the cortex and hippocampus.展开更多
OBJECTIVE To investigate the effects of osthole on learning and memory impairment of AD mice induced by injection of Aβ25-35 and the content of Ca2+, GLU and Aβ1-42 in the brain tissue and peripheral blood. METHODS ...OBJECTIVE To investigate the effects of osthole on learning and memory impairment of AD mice induced by injection of Aβ25-35 and the content of Ca2+, GLU and Aβ1-42 in the brain tissue and peripheral blood. METHODS Mice were randomly assigned to sham operation, Aβ25-35, Aβ25-35+Ost-L,Aβ25-35+Ost-M, and Aβ25-35+Ost-H group. Water maze test was performed to assessing spatial learning ability of mice. It is determined that the MDA level and the activity of SOD in the brain tissue of mice in each group by colorimetry. The GLU kit and Ca2 +kit were used to detect the GLU, Ca2 +in tissue and serum. ELISA was used to detect the expression of Aβ1-42 in the hippocampus and serum of mice. HE staining and silver staining were used to detect neuron apoptosis and pathological changes in brain slices and so on. RESULTS(1) Effects of osthole on learning and memory: With the increase of training day,the escape latencies continuously reduced in each experimental group, the escape latencies of the model group was longer on the 1 st, 2 nd, 3 rd, and 5 thdays than the normal group, the difference was statistically significant(day 3 and 4: P<0.05, day 5: P<0.01);compared with the model group, the escaping latency on the 5 thday of the OST low-medium high-dose group was significantly shortened, which was statistically significant(P<0.05).(2) Effects on oxidative stresspathway: the SOD activity of AD mice in the hippocampus model group was lower than that in the normal group, which was statistically significant(P<0.05);The SOD activity in the OST group was higher than that in the model group, which was statistically significant(P<0.05). The MDA content in the model group was significantly higher than that in the normal group(P<0.05). The MDA content in the OST high-dose group was lower than that in the model group, which was statistically significant(P<0.05).(3) Effects of GLU levels on neurotransmitters:the results of the detection of GLU in cortical area and GLU in serum of AD mice in OST dose groups showed that serum GLU levels in the model group were significantly lower than those in the sham group, which was statistically significant(P<0.05). GLU levels in the cortical area were also significantly higher than those in the sham group, which was statistically significant(P<0.05). Compared with the model group, GLU levels in the OST administration group were significantly down-regulated. Among the serum, the effect of medium dose group was obvious. Although there was a trend of down-regulation in the cortical administration group, there was no statistical significance.(4) Changes in Ca2+concentration in the brain. Detection of intracellular Ca2 +concentration in AD mice by OST doses showed that,compared with the sham group, the model group was significantly upregulated in cortical Ca2 +levels.There was no statistical difference in the administration group. Compared with the model group, the concentration of Ca2+in the OST-H group significantly decreased.(5) Effect on levels of Aβ1-42 in hippocampus and serum: model group had significantly higher Aβ1-42 levels in hippocampus than in sham operation group, which was statistically significant(P<0.05). Aβ1-42 in serum was also significantly upregulated compared to the sham group, which was statistically significant(P<0.05). Compared with the model group, the levels of Aβ1-42 in the OST administration group were significantly down-regulated,with the lower and middle doses in the hippocampus being more significant, while the serum was more pronounced at lower doses.(6) Silver staining to detect the tangles of hippocampal neurons: Neuron tangles in the hippocampal CA1 region showed a dark brown-yellow granule distribution in the nuclei of the model group(positive expression). Nerve cell body and dendrites, axons are black or black red,background light yellow. Compared with the model group, the administration group has improved significantly. CONCLUSION OST improves spatial learning and memory of dementia model mice injected with Aβ25-35 in both hippocampus. Experimental studies have shown that OST has different degrees of regulation on neuronal apoptosis, Ca2 +/GLU/oxidative stress and other pathways, and it plays a role in improving multiple AD pathological changes and delaying the pathogenesis of neurodegenerative diseases.展开更多
作为面向互联网资源共享的虚拟计算环境的实例,iVCE(Internet based virtual computing environment)for Memory致力于解决广域分布的内存资源的共享与综合利用问题.由于内存资源的特殊性,传统的资源管理方法很难适用.以iVCE for Memor...作为面向互联网资源共享的虚拟计算环境的实例,iVCE(Internet based virtual computing environment)for Memory致力于解决广域分布的内存资源的共享与综合利用问题.由于内存资源的特殊性,传统的资源管理方法很难适用.以iVCE for Memory作为背景,提出一种基于聚类的虚拟计算环境资源聚合方法,有效降低了资源聚合的问题规模;借鉴物理学中的力场和势能理论,建立了实现资源聚合的基本模型和力场-势能模型以及相应的分布式算法;通过基于真实网络拓扑的模拟,对两种模型和算法分别进行了评估和验证.展开更多
文摘OBJECTIVE To investigate the effects of imperatorin on the spatial learning memory impairment and neuroinflammation in model mice of Alzheimer disease(AD)induced by intracerebroventricular injection of Aβ1-42.METHODS Mouse model of AD was established by injection of Aβ1-42 into the lateral ventricles.Im⁃peratorin(2.5 and 5.0 mg·kg-1,daily)was inject⁃ed by intraperitoneally 1 h after intracerebroven⁃tricular injection for 13 d.The effect of imperato⁃rin on the spatial learning and memory impair⁃ment was assessed by eight arm maze tests.The levels of cytokines TNF-α,IL-1β,IL-6,IL-18 and chemokines MCP-1 in mouse cortex and hip⁃pocampus were detected by ELISA.The protein expression of NF-κB P65,TLR4,MyD88,p-P38,p-ERK,and p-JNK were detected by Western blotting.RESULTS As compared with the AD model group,imperatorin treatment significantly attenuated Aβ1-42-induced spatial learning and memory impairment assessed by eight arm maze tests.In addition,imperatorin significantly reduced the levels of cytokines TNF-α,IL-1β,IL-6,IL-18 and chemokines MCP-1 in the cerebral cortex and hippocampus.Meanwhile,Western blotting results showed that imperatorin treat⁃ment significantly down-regulated the protein expression of NF-κB P65,TLR4,MyD88,p-P38,p-ERK,and p-JNK.CONCLUSION Imperatorin has neuroprotective effects in the Aβ1-42 induced AD model mice and its mechanism may be partially associated with the inhibition of inflam⁃matory response in the cortex and hippocampus.
基金National Natural Science Foundation of China(81703901)Shandong Province Natural Science Foundation of China(ZR2016HB56)
文摘OBJECTIVE To investigate the effects of osthole on learning and memory impairment of AD mice induced by injection of Aβ25-35 and the content of Ca2+, GLU and Aβ1-42 in the brain tissue and peripheral blood. METHODS Mice were randomly assigned to sham operation, Aβ25-35, Aβ25-35+Ost-L,Aβ25-35+Ost-M, and Aβ25-35+Ost-H group. Water maze test was performed to assessing spatial learning ability of mice. It is determined that the MDA level and the activity of SOD in the brain tissue of mice in each group by colorimetry. The GLU kit and Ca2 +kit were used to detect the GLU, Ca2 +in tissue and serum. ELISA was used to detect the expression of Aβ1-42 in the hippocampus and serum of mice. HE staining and silver staining were used to detect neuron apoptosis and pathological changes in brain slices and so on. RESULTS(1) Effects of osthole on learning and memory: With the increase of training day,the escape latencies continuously reduced in each experimental group, the escape latencies of the model group was longer on the 1 st, 2 nd, 3 rd, and 5 thdays than the normal group, the difference was statistically significant(day 3 and 4: P<0.05, day 5: P<0.01);compared with the model group, the escaping latency on the 5 thday of the OST low-medium high-dose group was significantly shortened, which was statistically significant(P<0.05).(2) Effects on oxidative stresspathway: the SOD activity of AD mice in the hippocampus model group was lower than that in the normal group, which was statistically significant(P<0.05);The SOD activity in the OST group was higher than that in the model group, which was statistically significant(P<0.05). The MDA content in the model group was significantly higher than that in the normal group(P<0.05). The MDA content in the OST high-dose group was lower than that in the model group, which was statistically significant(P<0.05).(3) Effects of GLU levels on neurotransmitters:the results of the detection of GLU in cortical area and GLU in serum of AD mice in OST dose groups showed that serum GLU levels in the model group were significantly lower than those in the sham group, which was statistically significant(P<0.05). GLU levels in the cortical area were also significantly higher than those in the sham group, which was statistically significant(P<0.05). Compared with the model group, GLU levels in the OST administration group were significantly down-regulated. Among the serum, the effect of medium dose group was obvious. Although there was a trend of down-regulation in the cortical administration group, there was no statistical significance.(4) Changes in Ca2+concentration in the brain. Detection of intracellular Ca2 +concentration in AD mice by OST doses showed that,compared with the sham group, the model group was significantly upregulated in cortical Ca2 +levels.There was no statistical difference in the administration group. Compared with the model group, the concentration of Ca2+in the OST-H group significantly decreased.(5) Effect on levels of Aβ1-42 in hippocampus and serum: model group had significantly higher Aβ1-42 levels in hippocampus than in sham operation group, which was statistically significant(P<0.05). Aβ1-42 in serum was also significantly upregulated compared to the sham group, which was statistically significant(P<0.05). Compared with the model group, the levels of Aβ1-42 in the OST administration group were significantly down-regulated,with the lower and middle doses in the hippocampus being more significant, while the serum was more pronounced at lower doses.(6) Silver staining to detect the tangles of hippocampal neurons: Neuron tangles in the hippocampal CA1 region showed a dark brown-yellow granule distribution in the nuclei of the model group(positive expression). Nerve cell body and dendrites, axons are black or black red,background light yellow. Compared with the model group, the administration group has improved significantly. CONCLUSION OST improves spatial learning and memory of dementia model mice injected with Aβ25-35 in both hippocampus. Experimental studies have shown that OST has different degrees of regulation on neuronal apoptosis, Ca2 +/GLU/oxidative stress and other pathways, and it plays a role in improving multiple AD pathological changes and delaying the pathogenesis of neurodegenerative diseases.
基金the National Natural Science Foundation of Chinaunder Grant Nos.6067316790412011(国家自然科学基金)the National Basic Research Program of Chinaunder GrantNo.2005CB321801(国家重点基础研究发展计划(973))
文摘作为面向互联网资源共享的虚拟计算环境的实例,iVCE(Internet based virtual computing environment)for Memory致力于解决广域分布的内存资源的共享与综合利用问题.由于内存资源的特殊性,传统的资源管理方法很难适用.以iVCE for Memory作为背景,提出一种基于聚类的虚拟计算环境资源聚合方法,有效降低了资源聚合的问题规模;借鉴物理学中的力场和势能理论,建立了实现资源聚合的基本模型和力场-势能模型以及相应的分布式算法;通过基于真实网络拓扑的模拟,对两种模型和算法分别进行了评估和验证.
