Objective To investigate the neuroprotective action of astragaloside Ⅳ(AS-Ⅳ) on spatial learning and memory impairment induced by amyloid-beta 1-42(Aβ1-42) in rats and elucidate its underlying molecular mechanisms....Objective To investigate the neuroprotective action of astragaloside Ⅳ(AS-Ⅳ) on spatial learning and memory impairment induced by amyloid-beta 1-42(Aβ1-42) in rats and elucidate its underlying molecular mechanisms.Methods Adult-male Sprague-Dawley rats(230-250 g) were divided into six groups randomly: control, Aβ1-42, AS-Ⅳ, Aβ1-42 plus 5 mg/kg·d AS-Ⅳ, Aβ1-42 plus 25 mg/kg·d AS-Ⅳ, and Aβ1-42 plus 50 mg/kg·d AS-Ⅳ groups. Aβ1-42 were delivered by intracerebroventricular injection under the guidance of a brain stereotaxic apparatus. The Morris water maze test(hidden platform test, probe trials, visible platform test) was performed one week after Aβ1-42 injection to obtain the ability of rat spatial learning and memory. AS-Ⅳ(5, 25 and 50 mg/kg·d) was administrated intraperitoneally once per day from the 8 th day after Aβ1-42 injection for 5 consecutive days. Average escape latencies, distances for searching for the platform under water and the percentage of total time elapsed and distance swam in the right quadrant after removing platform were determined by behavior softwaresystem. The vision and swim speeds of rats were also determined to exclude the effect of these factors on the parameters of learning and memory. After behavioral tests, the rats were sacrificed immediately by decapitation. Hippocampus were collected. The enzyme activities of superoxide dismutase(SOD), glutathione peroxidase(GSH-px) and catalase(CAT) in the hippocampus obtained from different-treated rat brain were measured by following the manufacturer’s instructions. The levels of interleukin-1 beta(IL-1β) and tumor necrosis factor-alpha(TNF-α) in tissue lysates were assayed with ELISA.Results The water maze test results indicated that chronic treatments with AS-Ⅳ effectively protected the rats from Aβ1-42-induced spatial learning and memory impairment. Furthermore, the activities of SOD, GSH-px and CAT decreased by Aβ1-42 were also restored by AS-Ⅳ treatment in the hippocampus of rats. In addition, AS-Ⅳ signi展开更多
A coralloid 3D g-C_(3)N_(4)supported VO_(2)catalyst was successfully synthesized in-situ by one-pot method,avoiding the agglomeration of VO_(2)during the reaction.The morphological and compositional information of the...A coralloid 3D g-C_(3)N_(4)supported VO_(2)catalyst was successfully synthesized in-situ by one-pot method,avoiding the agglomeration of VO_(2)during the reaction.The morphological and compositional information of the supported catalyst were investigated detailedly.30%VO_(2)/3D g-C_(3)N_(4)revealed excellent catalytic activity in aerobic oxidative desulfurization,the oxidative of dibenzothiophene(DBT),4-methyldibenzothiophene(4-MDBT)and 4,6-dimethyldibenzothiophene(4,6-DMDBT)reached 98.6%,99%and 99.4%,respectively,under the same mild conditions.The recycling performance and the mechanism on the oxidative of DBT were studied as well.展开更多
A plethora of evidence suggests that protein misfolding and aggregation are underlying mechanisms of various neurodegenerative diseases,such as prion diseases and Alzheimer's disease(AD).Like prion diseases,AD has...A plethora of evidence suggests that protein misfolding and aggregation are underlying mechanisms of various neurodegenerative diseases,such as prion diseases and Alzheimer's disease(AD).Like prion diseases,AD has been considered as an infectious disease in the past decades as it shows strain specificity and transmission potential.Although it remains elusive how protein aggregation leads to AD,it is becoming clear that cellular prion protein(PrP^c)plays an important role in AD pathogenesis.Here,we briefly reviewed AD pathogenesis and focused on recent progresses how PrP^c contributed to AD development.In addition,we proposed a potential mechanism to explain why infectious agents,such as viruses,conduce AD pathogenesis.Microbe infections cause AD deposition and upregulation of PrP^c,which lead to high affinity binding between AD oligomers and PrP^c.The interaction between PrP^c and AP oligomers in turn activates the Fyn signaling cascade,resulting in neuron death in the central nervous system(CNS).Thus,silencing PrP^c expression may turn out be an effective treatment for PrP^c dependent AD.展开更多
Background The current diagnosis of Alzheimer’s disease(AD)is based on a series of analyses which involve clinical,instrumental and laboratory findings.However,signs,symptoms and biomarker alterations observed in AD ...Background The current diagnosis of Alzheimer’s disease(AD)is based on a series of analyses which involve clinical,instrumental and laboratory findings.However,signs,symptoms and biomarker alterations observed in AD might overlap with other dementias,resulting in misdiagnosis.Methods Here we describe a new diagnostic approach for AD which takes advantage of the boosted sensitivity in biomolecular detection,as allowed by seed amplification assay(SAA),combined with the unique specificity in biomolecular recognition,as provided by surface-enhanced Raman spectroscopy(SERS).Results The SAA-SERS approach supported by machine learning data analysis allowed efficient identification of pathological Aβoligomers in the cerebrospinal fluid of patients with a clinical diagnosis of AD or mild cognitive impairment due to AD.Conclusions Such analytical approach can be used to recognize disease features,thus allowing early stratification and selection of patients,which is fundamental in clinical treatments and pharmacological trials.展开更多
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
Previous studies indicate that memantine, a low-affinity N-methyI-D-aspartate receptor antagonist exerted acute protective effects against amyloid-β protein-induced neurotoxicity. In the present study, the chronic ef...Previous studies indicate that memantine, a low-affinity N-methyI-D-aspartate receptor antagonist exerted acute protective effects against amyloid-β protein-induced neurotoxicity. In the present study, the chronic effects and mechanisms of memantine were investigated further using electrophysiological methods. The results showed that 7-day intraperitoneal application of memantine, at doses of 5 mg/kg or 20 mg/kg, did not alter hippocampal long-term potentiation induction in rats, while 40 mg/kg memantine presented potent long-term potentiation inhibition. Then further in vitro studys were carried out in 5 mg/kg and 20 mg/kg memantine treated rats. We found that 20 mg/kg memantine attenuated the potent long-term potentiation inhibition caused by exposure to amyloid-β protein in the dentate gyrus in vitro. These findings are the first to demonstrate the antagonizing effect of long-term systematic treatment of memantine against amyloid-β protein triggered long-term potentiation inhibition to improve synaptic plasticity.展开更多
基金Supported by the Natural Science Foundation of Shaanxi Province of China(2015JQ8299)National Science Foundation of China(81703842)Traditional Chinese Medicine Scientific Research Projects of Shaanxi Province of China(JCMS032)
文摘Objective To investigate the neuroprotective action of astragaloside Ⅳ(AS-Ⅳ) on spatial learning and memory impairment induced by amyloid-beta 1-42(Aβ1-42) in rats and elucidate its underlying molecular mechanisms.Methods Adult-male Sprague-Dawley rats(230-250 g) were divided into six groups randomly: control, Aβ1-42, AS-Ⅳ, Aβ1-42 plus 5 mg/kg·d AS-Ⅳ, Aβ1-42 plus 25 mg/kg·d AS-Ⅳ, and Aβ1-42 plus 50 mg/kg·d AS-Ⅳ groups. Aβ1-42 were delivered by intracerebroventricular injection under the guidance of a brain stereotaxic apparatus. The Morris water maze test(hidden platform test, probe trials, visible platform test) was performed one week after Aβ1-42 injection to obtain the ability of rat spatial learning and memory. AS-Ⅳ(5, 25 and 50 mg/kg·d) was administrated intraperitoneally once per day from the 8 th day after Aβ1-42 injection for 5 consecutive days. Average escape latencies, distances for searching for the platform under water and the percentage of total time elapsed and distance swam in the right quadrant after removing platform were determined by behavior softwaresystem. The vision and swim speeds of rats were also determined to exclude the effect of these factors on the parameters of learning and memory. After behavioral tests, the rats were sacrificed immediately by decapitation. Hippocampus were collected. The enzyme activities of superoxide dismutase(SOD), glutathione peroxidase(GSH-px) and catalase(CAT) in the hippocampus obtained from different-treated rat brain were measured by following the manufacturer’s instructions. The levels of interleukin-1 beta(IL-1β) and tumor necrosis factor-alpha(TNF-α) in tissue lysates were assayed with ELISA.Results The water maze test results indicated that chronic treatments with AS-Ⅳ effectively protected the rats from Aβ1-42-induced spatial learning and memory impairment. Furthermore, the activities of SOD, GSH-px and CAT decreased by Aβ1-42 were also restored by AS-Ⅳ treatment in the hippocampus of rats. In addition, AS-Ⅳ signi
基金the financial support from National Natural Science Foundation of China(21808091 and 22178154)supported by the Student Innovation and Entrepreneurship Training Program(202210299640X)。
文摘A coralloid 3D g-C_(3)N_(4)supported VO_(2)catalyst was successfully synthesized in-situ by one-pot method,avoiding the agglomeration of VO_(2)during the reaction.The morphological and compositional information of the supported catalyst were investigated detailedly.30%VO_(2)/3D g-C_(3)N_(4)revealed excellent catalytic activity in aerobic oxidative desulfurization,the oxidative of dibenzothiophene(DBT),4-methyldibenzothiophene(4-MDBT)and 4,6-dimethyldibenzothiophene(4,6-DMDBT)reached 98.6%,99%and 99.4%,respectively,under the same mild conditions.The recycling performance and the mechanism on the oxidative of DBT were studied as well.
基金supported by National Natural Science Foundation of China (31670170 and 31270209)by Ministry monomer, GAG facilitates Aβ fibrilization by pulling PrPC monomer to oligomerize
文摘A plethora of evidence suggests that protein misfolding and aggregation are underlying mechanisms of various neurodegenerative diseases,such as prion diseases and Alzheimer's disease(AD).Like prion diseases,AD has been considered as an infectious disease in the past decades as it shows strain specificity and transmission potential.Although it remains elusive how protein aggregation leads to AD,it is becoming clear that cellular prion protein(PrP^c)plays an important role in AD pathogenesis.Here,we briefly reviewed AD pathogenesis and focused on recent progresses how PrP^c contributed to AD development.In addition,we proposed a potential mechanism to explain why infectious agents,such as viruses,conduce AD pathogenesis.Microbe infections cause AD deposition and upregulation of PrP^c,which lead to high affinity binding between AD oligomers and PrP^c.The interaction between PrP^c and AP oligomers in turn activates the Fyn signaling cascade,resulting in neuron death in the central nervous system(CNS).Thus,silencing PrP^c expression may turn out be an effective treatment for PrP^c dependent AD.
基金supported in part by the Italian Ministry of Health(RRC,5M-2018-23680266,and GR-2021-12372019)to FMthe European Community,Italian Ministry of Education,University and Research and the Italian Ministry of Health within the EuroNanoMed3 ERANET cofund SPEEDY project and by Tuscany Region(FAS-Salute 2018)project PRAMA to PM and to FM.
文摘Background The current diagnosis of Alzheimer’s disease(AD)is based on a series of analyses which involve clinical,instrumental and laboratory findings.However,signs,symptoms and biomarker alterations observed in AD might overlap with other dementias,resulting in misdiagnosis.Methods Here we describe a new diagnostic approach for AD which takes advantage of the boosted sensitivity in biomolecular detection,as allowed by seed amplification assay(SAA),combined with the unique specificity in biomolecular recognition,as provided by surface-enhanced Raman spectroscopy(SERS).Results The SAA-SERS approach supported by machine learning data analysis allowed efficient identification of pathological Aβoligomers in the cerebrospinal fluid of patients with a clinical diagnosis of AD or mild cognitive impairment due to AD.Conclusions Such analytical approach can be used to recognize disease features,thus allowing early stratification and selection of patients,which is fundamental in clinical treatments and pharmacological trials.
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 the National Natural Science Foundation of China,No.81070873,30970932Ningbo Natural Science Foundation,No.2011A610065,2010A610072,2011A610064,2011C51006the Scientific Research Fund of Zhejiang Provincial Education Department,No.Y201018164
文摘Previous studies indicate that memantine, a low-affinity N-methyI-D-aspartate receptor antagonist exerted acute protective effects against amyloid-β protein-induced neurotoxicity. In the present study, the chronic effects and mechanisms of memantine were investigated further using electrophysiological methods. The results showed that 7-day intraperitoneal application of memantine, at doses of 5 mg/kg or 20 mg/kg, did not alter hippocampal long-term potentiation induction in rats, while 40 mg/kg memantine presented potent long-term potentiation inhibition. Then further in vitro studys were carried out in 5 mg/kg and 20 mg/kg memantine treated rats. We found that 20 mg/kg memantine attenuated the potent long-term potentiation inhibition caused by exposure to amyloid-β protein in the dentate gyrus in vitro. These findings are the first to demonstrate the antagonizing effect of long-term systematic treatment of memantine against amyloid-β protein triggered long-term potentiation inhibition to improve synaptic plasticity.
