Repetitive transcranial magnetic stimulation （rTMS） is a non-invasive treatment that can enhance the recovery of neurological function after stroke. Whether it can similarly promote the recovery of cognitive functio...Repetitive transcranial magnetic stimulation （rTMS） is a non-invasive treatment that can enhance the recovery of neurological function after stroke. Whether it can similarly promote the recovery of cognitive function after vascular dementia remains unknown, In this study, a rat model for vascular dementia was established by the two-vessel occlusion method. Two days after injury, 30 pulses of rTMS were ad- ministered to each cerebral hemisphere at a frequency of 0.5 Hz and a magnetic field intensity of 1,33 T. The Morris water maze test was used to evaluate learning and memory function. The Karnovsky-Roots method was performed to determine the density of cholinergic neurons in the hippocampal CA1 region. Immunohistochemical staining was used to determine the number of brain-derived neurotroph- ic factor （BDNF）-immunoreactive cells in the hippocampal CA1 region, rTMS treatment for 30 days significantly improved learning and memory function, increased acetylcholinesterase and choline acetyltransferase activity, increased the density of cholinergic neurons, and increased the number of BDNF-immunoreactive cells. These results indicate that rTMS can ameliorate learning and memory deficiencies in rats with vascular dementia, The mechanism through which this occurs might be related to the promotion of BDNF expression and subsequent restoration of cholinergic system activity in hippocampal CA 1 region.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 展开更多
Ginsenoside Rb1 has been reported to exert anti-aging and anti-neurodegenerative effects. In the present study, we investigate whether ginsenoside Rb1 is involved in neurite outgrowth and neuroprotection against damag...Ginsenoside Rb1 has been reported to exert anti-aging and anti-neurodegenerative effects. In the present study, we investigate whether ginsenoside Rb1 is involved in neurite outgrowth and neuroprotection against damage induced by amyloid beta（25–35） in cultured hippocampal neurons, and explore the underlying mechanisms. Ginsenoside Rb1 significantly increased neurite outgrowth in hippocampal neurons, and increased the expression of phosphorylated-Akt and phosphorylated extracellular signal-regulated kinase 1/2. These effects were abrogated by API-2 and PD98059, inhibitors of the signaling proteins Akt and MEK. Additionally, cultured hippocampal neurons were exposed to amyloid beta（25–35） for 30 minutes; ginsenoside Rb1 prevented apoptosis induced by amyloid beta（25–35）, and this effect was blocked by API-2 and PD98059. Furthermore, ginsenoside Rb1 significantly reversed the reduction in phosphorylated-Akt and phosphorylated extracellular signal-regulated kinase 1/2 levels induced by amyloid beta（25–35）, and API-2 neutralized the effect of ginsenoside Rb1. The present results indicate that ginsenoside Rb1 enhances neurite outgrowth and protects against neurotoxicity induced by amyloid beta（25–35） via a mechanism involving Akt and extracellular signal-regulated kinase 1/2 signaling.展开更多
Hippocampal morphological change is one of the main hallmarks of Alzheimer’s disease(AD).However,whether hippocampal radiomic features are robust as predictors of progression from mild cognitive impairment(MCI)to AD ...Hippocampal morphological change is one of the main hallmarks of Alzheimer’s disease(AD).However,whether hippocampal radiomic features are robust as predictors of progression from mild cognitive impairment(MCI)to AD dementia and whether these features provide any neurobiological foundation remains unclear.The primary aim of this study was to verify whether hippocampal radiomic features can serve as robust magnetic resonance imaging(MRI)markers for AD.Multivariate classifier-based support vector machine(SVM)analysis provided individual-level predictions for distinguishing AD patients(n=261)from normal controls(NCs;n=231)with an accuracy of 88.21%and intersite crossvalidation.Further analyses of a large,independent the Alzheimer’s Disease Neuroimaging Initiative(ADNI)dataset(n=1228)reinforced these findings.In MCI groups,a systemic analysis demonstrated that the identified features were significantly associated with clinical features(e.g.,apolipoprotein E(APOE)genotype,polygenic risk scores,cerebrospinal fluid(CSF)Ab,CSF Tau),and longitudinal changes in cognition ability;more importantly,the radiomic features had a consistently altered pattern with changes in the MMSE scores over 5 years of follow-up.These comprehensive results suggest that hippocampal radiomic features can serve as robust biomarkers for clinical application in AD/MCI,and further provide evidence for predicting whether an MCI subject would convert to AD based on the radiomics of the hippocampus.The results of this study are expected to have a substantial impact on the early diagnosis of AD/MCI.展开更多
This study established an aged rat model of cognitive dysfunction using anesthesia with 2% iso- flurane and 80% oxygen for 2 hours. Twenty-four hours later, Y-maze test results showed that isoflurane significantly imp...This study established an aged rat model of cognitive dysfunction using anesthesia with 2% iso- flurane and 80% oxygen for 2 hours. Twenty-four hours later, Y-maze test results showed that isoflurane significantly impaired cognitive function in aged rats. Gas chromatography-mass spectrometry results showed that isoflurane also significantly increased the levels of N,N-diethy- lacetamide, n-ethylacetamide, aspartic acid, malic acid and arabinonic acid in the hippocampus of isoflurane-treated rats. Moreover, aspartic acid, N,N-diethylacetamide, n-ethylacetamide and malic acid concentration was positively correlated with the degree of cognitive dysfunction in the isoflurane-treated rats. It is evident that hippocampal metabolite changes are involved in the formation of cognitive dysfunction after isoflurane anesthesia. To further verify these results, this study cultured hippocampal neurons in vitro, which were then treated with aspartic acid （100 μmol/L）. Results suggested that aspartic acid concentration in the hippocampus may be a biomarker for predicting the occurrence and disease progress of cognitive dysfunction.展开更多
基金supported by a grant from the Major Project of Educational Commission of Hubei Province of China,No.D20152101
文摘Repetitive transcranial magnetic stimulation （rTMS） is a non-invasive treatment that can enhance the recovery of neurological function after stroke. Whether it can similarly promote the recovery of cognitive function after vascular dementia remains unknown, In this study, a rat model for vascular dementia was established by the two-vessel occlusion method. Two days after injury, 30 pulses of rTMS were ad- ministered to each cerebral hemisphere at a frequency of 0.5 Hz and a magnetic field intensity of 1,33 T. The Morris water maze test was used to evaluate learning and memory function. The Karnovsky-Roots method was performed to determine the density of cholinergic neurons in the hippocampal CA1 region. Immunohistochemical staining was used to determine the number of brain-derived neurotroph- ic factor （BDNF）-immunoreactive cells in the hippocampal CA1 region, rTMS treatment for 30 days significantly improved learning and memory function, increased acetylcholinesterase and choline acetyltransferase activity, increased the density of cholinergic neurons, and increased the number of BDNF-immunoreactive cells. These results indicate that rTMS can ameliorate learning and memory deficiencies in rats with vascular dementia, The mechanism through which this occurs might be related to the promotion of BDNF expression and subsequent restoration of cholinergic system activity in hippocampal CA 1 region.
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
基金supported by grants from the National Natural Science Foundation of China,No.30971531,81070987
文摘Ginsenoside Rb1 has been reported to exert anti-aging and anti-neurodegenerative effects. In the present study, we investigate whether ginsenoside Rb1 is involved in neurite outgrowth and neuroprotection against damage induced by amyloid beta（25–35） in cultured hippocampal neurons, and explore the underlying mechanisms. Ginsenoside Rb1 significantly increased neurite outgrowth in hippocampal neurons, and increased the expression of phosphorylated-Akt and phosphorylated extracellular signal-regulated kinase 1/2. These effects were abrogated by API-2 and PD98059, inhibitors of the signaling proteins Akt and MEK. Additionally, cultured hippocampal neurons were exposed to amyloid beta（25–35） for 30 minutes; ginsenoside Rb1 prevented apoptosis induced by amyloid beta（25–35）, and this effect was blocked by API-2 and PD98059. Furthermore, ginsenoside Rb1 significantly reversed the reduction in phosphorylated-Akt and phosphorylated extracellular signal-regulated kinase 1/2 levels induced by amyloid beta（25–35）, and API-2 neutralized the effect of ginsenoside Rb1. The present results indicate that ginsenoside Rb1 enhances neurite outgrowth and protects against neurotoxicity induced by amyloid beta（25–35） via a mechanism involving Akt and extracellular signal-regulated kinase 1/2 signaling.
基金partially supported by the National Key Research and Development Program of China (2016YFC1305904)the National Natural Science Foundation of China (81871438, 81901101, 61633018, 81571062, 81400890, 81871398)+10 种基金the Strategic Priority Research Program (B) of the Chinese Academy of Sciences (XDB32020200)the Beijing Municipal Science & Technology Commission (Z171100000117001, Z171100000117002)the Primary Research & Development Plan of Shandong Province (2017GGX10112)the Open Project Program of the National Laboratory of Pattern Recognition (NLPR) (201900021)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)funded by the National Institute on Agingthe National Institute of Biomedical Imaging and Bioengineeringgenerous contributions from Abb Vie, Alzheimer’s AssociationAlzheimer’s Drug Discovery FoundationThe Canadian Institutes of Health Research provide funds to support ADNI clinical sites in Canada。
文摘Hippocampal morphological change is one of the main hallmarks of Alzheimer’s disease(AD).However,whether hippocampal radiomic features are robust as predictors of progression from mild cognitive impairment(MCI)to AD dementia and whether these features provide any neurobiological foundation remains unclear.The primary aim of this study was to verify whether hippocampal radiomic features can serve as robust magnetic resonance imaging(MRI)markers for AD.Multivariate classifier-based support vector machine(SVM)analysis provided individual-level predictions for distinguishing AD patients(n=261)from normal controls(NCs;n=231)with an accuracy of 88.21%and intersite crossvalidation.Further analyses of a large,independent the Alzheimer’s Disease Neuroimaging Initiative(ADNI)dataset(n=1228)reinforced these findings.In MCI groups,a systemic analysis demonstrated that the identified features were significantly associated with clinical features(e.g.,apolipoprotein E(APOE)genotype,polygenic risk scores,cerebrospinal fluid(CSF)Ab,CSF Tau),and longitudinal changes in cognition ability;more importantly,the radiomic features had a consistently altered pattern with changes in the MMSE scores over 5 years of follow-up.These comprehensive results suggest that hippocampal radiomic features can serve as robust biomarkers for clinical application in AD/MCI,and further provide evidence for predicting whether an MCI subject would convert to AD based on the radiomics of the hippocampus.The results of this study are expected to have a substantial impact on the early diagnosis of AD/MCI.
基金supported by the National Natural Science Foundation of China,No.30871306
文摘This study established an aged rat model of cognitive dysfunction using anesthesia with 2% iso- flurane and 80% oxygen for 2 hours. Twenty-four hours later, Y-maze test results showed that isoflurane significantly impaired cognitive function in aged rats. Gas chromatography-mass spectrometry results showed that isoflurane also significantly increased the levels of N,N-diethy- lacetamide, n-ethylacetamide, aspartic acid, malic acid and arabinonic acid in the hippocampus of isoflurane-treated rats. Moreover, aspartic acid, N,N-diethylacetamide, n-ethylacetamide and malic acid concentration was positively correlated with the degree of cognitive dysfunction in the isoflurane-treated rats. It is evident that hippocampal metabolite changes are involved in the formation of cognitive dysfunction after isoflurane anesthesia. To further verify these results, this study cultured hippocampal neurons in vitro, which were then treated with aspartic acid （100 μmol/L）. Results suggested that aspartic acid concentration in the hippocampus may be a biomarker for predicting the occurrence and disease progress of cognitive dysfunction.
