Bone marrow mesenchymal stem cells were isolated, purified and cultured in vitro by Percoll density gradient centrifugation combined with the cell adherence method. Passages 3 5 bone marrow mesenchymal stem cells were...Bone marrow mesenchymal stem cells were isolated, purified and cultured in vitro by Percoll density gradient centrifugation combined with the cell adherence method. Passages 3 5 bone marrow mesenchymal stem cells were transplanted into rats with traumatic spinal cord injury via the caudal vein. Basso-Beattie-Bresnahan scores indicate that neurological function of experimental rats was significantly improved over transplantation time （1-5 weeks）. Expressions of choline acetyltransferase, glutamic acid decarboxytase and synapsins in the damaged spinal cord of rats was significantly increased after transplantation, determined by immunofluorescence staining and laser confocal scanning microscopy. Bone marrow mesenchymal stem cells that had migrated into the damaged area of rats in the experimental group began to express choline acetyltransferase, glutamic acid decarboxylase and synapsins, 3 weeks after transplantation. The Basso-Beattie- Bresnahan scores positively correlated with expression of choline acetyltransferase and synapsins. Experimental findings indicate that intravenously transplanted bone marrow mesenchymal stem cells traverse into the damaged spinal cord of rats, promote expression of choline acetyltransferase, glutamic acid decarboxylase and synapsins, and improve nerve function in rats with spinal cord injury.展开更多
Synapsins serve as flagships among the presynaptic proteins due to their abundance on synaptic vesicles and contribution to synaptic communication. Several studies have emphasized the importance of this multi-gene fam...Synapsins serve as flagships among the presynaptic proteins due to their abundance on synaptic vesicles and contribution to synaptic communication. Several studies have emphasized the importance of this multi-gene family of neuron-specific phosphoproteins in maintaining brain physiology. In the recent times, increasing evidence has established the relevance of alterations in synapsins as a major determinant in many neurological disorders. Here,we give a comprehensive description of the diverse roles of the synapsin family and the underlying molecular mechanisms that contribute to several neurological disorders.These physiologically important roles of synapsins associated with neurological disorders are just beginning to be understood. A detailed understanding of the diversified expression of synapsins may serve to strategize novel therapeutic approaches for these debilitating neurological disorders.展开更多
Xuefu Zhuyu decoction has been used for treating traumatic brain injury and improving post-traumatic dysfunction, but its mechanism of action needs further investigation. This study established rat models of traumatic...Xuefu Zhuyu decoction has been used for treating traumatic brain injury and improving post-traumatic dysfunction, but its mechanism of action needs further investigation. This study established rat models of traumatic brain injury by controlled cortical impact. Rat models were intragastrically administered 9 and 18 g/kg Xuefu Zhuyu decoction once a day for 14 or 21 days. Changes in neurological function were assessed by modified neurological severity scores and the Morris water maze. Immunohistochemistry, western blot assay, and re- verse-transcription polymerase chain reaction were used to analyze synapsin protein and mRNA expression at the injury site of rats. Our results showed that Xuefu Zhuyu decoction visibly improved neurological function of rats with traumatic brain injury. These changes were accompanied by increased expression of synaptophysin, synapsin I, and postsynaptic density protein-95 protein and mRNA in a dose-de- pendent manner. These findings indicate that Xuefu Zhuyu decoction increases synapsin expression and improves neurological deficits alder traumatic brain injury.展开更多
The Xingnao Jieyu capsule has been shown to effectively relieve neurologic impairments and les- sen depression. It remains poorly understood whether this capsule can be used to treat post-stroke depression. Thus, in t...The Xingnao Jieyu capsule has been shown to effectively relieve neurologic impairments and les- sen depression. It remains poorly understood whether this capsule can be used to treat post-stroke depression. Thus, in the present study, we established a rat model of post-stroke depression using left middle cerebral artery occlusions in combination of chronic unpredictable stress and solitary housing during development. Experimental rats received intragastric perfusion with 0.82, 0.41, and 0.20 g/kg Xingnao Jieyu capsules separately dissolved in 2 mL distilled water. Fluoxetine served as a positive control. The treatment was conducted over 28 days. Sugar water consumption test, open-field test, real-time fluorescent quantitative PCR and immunohistochemical staining results demonstrated that intragastric perfusion with various doses of Xingnao Jieyu capsules increased sugar water consumption, voluntary behaviors and synaptotagmin mRNA and protein expression in rats with post-stroke depression. These therapeutic effects were similar to those of fluoxetine. These results indicate that Xingnao Jieyu capsules upregulate synaptotagmin expression in hip pocampi of rats with post-stroke depression, and exert antidepressant effects.展开更多
Paired associative stimulation has been used in stroke patients as an innovative recovery treatment.However,the mechanisms underlying the therapeutic effectiveness of paired associative stimulation on neurological fun...Paired associative stimulation has been used in stroke patients as an innovative recovery treatment.However,the mechanisms underlying the therapeutic effectiveness of paired associative stimulation on neurological function remain unclear.In this study,rats were randomly divided into middle cerebral occlusion model(MCAO)and paired associated magnetic stimulation(PAMS)groups.The MCAO rat model was produced by middle cerebral artery embolization.The PAMS group received PAMS on days 3 to 20 post MCAO.The MCAO group received sham stimulation,three times every week.Within 18 days after ischemia,rats were subjected to behavioral experiments—the foot-fault test,the balance beam walking test,and the ladder walking test.Balance ability was improved on days 15 and 17,and the footfault rate was less in their affected limb on day 15 in the PAMS group compared with the MCAO group.Western blot assay showed that the expression levels of brain derived neurotrophic factor,glutamate receptor 2/3,postsynaptic density protein 95 and synapsin-1 were significantly increased in the PAMS group compared with the MCAO group in the ipsilateral sensorimotor cortex on day 21.Resting-state functional magnetic resonance imaging revealed that regional brain activities in the sensorimotor cortex were increased in the ipsilateral hemisphere,but decreased in the contralateral hemisphere on day 20.By finite element simulation,the electric field distribution showed a higher intensity,of approximately 0.4 A/m^2,in the ischemic cortex compared with the contralateral cortex in the template.Together,our findings show that PAMS upregulates neuroplasticity-related proteins,increases regional brain activity,and promotes functional recovery in the affected sensorimotor cortex in the rat MCAO model.The experiments were approved by the Institutional Animal Care and Use Committee of Fudan University,China(approval No.201802173 S)on March 3,2018.展开更多
Dendrite ramification affects synaptic strength and plays a crucial role in memory. Previous studies revealed a correlation between beta 2-adrenergic receptor dysfunction and Alzheimer＇s disease （AD）, although the ...Dendrite ramification affects synaptic strength and plays a crucial role in memory. Previous studies revealed a correlation between beta 2-adrenergic receptor dysfunction and Alzheimer＇s disease （AD）, although the mechanism involved is still poorly understood. The current study investigated the potential effect of the selective β2-adrenergic receptor antagonist, ICI 118551 （ICI）, on Aβ deposits and AD-related cognitive impairment. Morris water maze test results demonstrated that the performance of AD-transgenic （TG） mice treated with ICI （AD-TG/ICI） was significantly poorer compared with NaCl-treated AD-TG mice （AD-TG/NaCl）, suggesting that β2-adrenergic receptor blockage by ICI might reduce the learning and memory abilities of mice. Golgi staining and immunohistochemical staining revealed that blockage of the β2-adrenergic receptor by ICI treatment decreased the number of dendritic branches, and ICI treatment in AD-TG mice decreased the expression of hippocampal synaptophysin and synapsin 1. Western blot assay results showed that the blockage of β2-adrener- gic receptor increased amyloid-β accumulation by downregulating hippocampal a-secretase activity and increasing the phosphorylation of amyloid precursor protein. These findings suggest that blocking the β2-adrenergic receptor inhibits dendrite ramification of hippocampal neurons in a mouse model of AD.展开更多
Objective To investigate acrylamide （ACR）-induced subacute neurotoxic effects on the central nervous system （CNS） at the synapse level in rats. Methods Thirty-six Sprague Dawley （SD） rats were randomized into th...Objective To investigate acrylamide （ACR）-induced subacute neurotoxic effects on the central nervous system （CNS） at the synapse level in rats. Methods Thirty-six Sprague Dawley （SD） rats were randomized into three groups, （1） a 30 mg/kg ACR-treated group, （2） a 50 mg/kg ACR-treated group, and （3） a normal saline （NS）-treated control group. Body weight and neurological changes were recorded each day. At the end of the test, cerebral cortex and cerebellum tissues were harvested and viewed using light and electron microscopy. Additionally, the expression of Synapsin I and P-Synapsin I in the cerebral cortex and cerebellum were investigated. Results The 50 mg/kg ACR-treated rats showed a significant reduction in body weight compared with untreated individuals （P 〈 0.05）. Rats exposed to ACR showed a significant increase in gait scores compared with the NS control group （P 〈 0.05）. Histological examination indicated neuronal structural damage in the 50 mg/kg ACR treatment group. The active zone distance （AZD） and the nearest neighbor distance （NND） of synaptic vesicles in the cerebral cortex and cerebellum were increased in both the 30 mg/kg and 50 mg/kg ACR treatment groups. The ratio of the distribution of synaptic vesicles in the readily releasable pool （RRP） was decreased. Furthermore, the expression levels of Synapsin I and P-Synapsin I in the cerebral cortex and cerebellum were decreased in both the 30 mg/kg and 50 mg/kg ACR treatment groups. Conclusion Subacute ACR exposure contributes to neuropathy in the rat CNS. Functional damage of synaptic proteins and vesicles may be a mechanism of ACR neurotoxicity.展开更多
Impaired hippocampal neurogenesis is one of the early pathological features of Alzheimer＇s disease. Enhancing adult hippocampal neuro- genesis has been pursued as a potential therapeutic strategy for Alzheimer＇s dis...Impaired hippocampal neurogenesis is one of the early pathological features of Alzheimer＇s disease. Enhancing adult hippocampal neuro- genesis has been pursued as a potential therapeutic strategy for Alzheimer＇s disease. Recent studies have demonstrated that environmental novelty activates β2-adrenergic signaling and prevents the memory impairment induced by amyloid-β oligomers. Here, we hypothesized that β2-adrenoceptor activation would enhance neurogenesis and ameliorate memory deficits in Alzheimer＇s disease. To test this hypothe- sis, we investigated the effects and mechanisms of action of β2-adrenoceptor activation on neurogenesis and memory in amyloid precursor protein/presenilin 1 （APP/PS1） mice using the agonist clenbuterol （intraperitoneal injection, 2 mg/kg）. We found that β2-adrenoceptor ac- tivation enhanced hippocampal neurogenesis, ameliorated memory deficits, and increased dendritic branching and the density of dendritic spines, lhese effects were associated with the upregulation of postsynaptic density 95, synapsin 1 and synaptophysin in APP/PS1 mice. Furthermore, β2-adrenoceptor activation decreased cerebral amyloid plaques by decreasing APP phosphorylation at Thr668. These findings suggest that β2-adrenoceptor activation enhances neurogenesis and ameliorates memory deficits in APP/PS 1 mice.展开更多
Brain-derived neurotrophic factor （BDNF） promotes synaptic formation and functional maturation by upregulating synapsin expression in cortical and hippocampal neurons. However, it remains controversial whether BDNF ...Brain-derived neurotrophic factor （BDNF） promotes synaptic formation and functional maturation by upregulating synapsin expression in cortical and hippocampal neurons. However, it remains controversial whether BDNF affects synapsin expression in spinal cord anterior horn neurons. Wistar rat spinal cord anterior horn neurons were cultured in serum-supplemented medium containing BDNF, BDNF antibody, and Hank＇s solution for 3 days, and then synapsin I and synaptophysin protein and mRNA expression was detected. Under serum-supplemented conditions the number of surviving neurons in the spinal cord anterior horn was similar among BDNF, anti-BDNF, and control groups （P 〉 0.05）. Synapsin I and synaptophysin protein and mRNA expressions were increased in BDNF-treated neurons, but decreased in BDNF antibody-treated neurons （P 〈 0.01）. These results indicated that BDNF significantly promotes synapsin I and synaptophysin expression in in vitro-cultured rat spinal cord anterior horn neurons.展开更多
基金supported by the Doctoral Fund of Ministry of Education of China,No.20060392003Academic Development Foundation of Fujian Medical University, No.JS08004
文摘Bone marrow mesenchymal stem cells were isolated, purified and cultured in vitro by Percoll density gradient centrifugation combined with the cell adherence method. Passages 3 5 bone marrow mesenchymal stem cells were transplanted into rats with traumatic spinal cord injury via the caudal vein. Basso-Beattie-Bresnahan scores indicate that neurological function of experimental rats was significantly improved over transplantation time （1-5 weeks）. Expressions of choline acetyltransferase, glutamic acid decarboxytase and synapsins in the damaged spinal cord of rats was significantly increased after transplantation, determined by immunofluorescence staining and laser confocal scanning microscopy. Bone marrow mesenchymal stem cells that had migrated into the damaged area of rats in the experimental group began to express choline acetyltransferase, glutamic acid decarboxylase and synapsins, 3 weeks after transplantation. The Basso-Beattie- Bresnahan scores positively correlated with expression of choline acetyltransferase and synapsins. Experimental findings indicate that intravenously transplanted bone marrow mesenchymal stem cells traverse into the damaged spinal cord of rats, promote expression of choline acetyltransferase, glutamic acid decarboxylase and synapsins, and improve nerve function in rats with spinal cord injury.
文摘Synapsins serve as flagships among the presynaptic proteins due to their abundance on synaptic vesicles and contribution to synaptic communication. Several studies have emphasized the importance of this multi-gene family of neuron-specific phosphoproteins in maintaining brain physiology. In the recent times, increasing evidence has established the relevance of alterations in synapsins as a major determinant in many neurological disorders. Here,we give a comprehensive description of the diverse roles of the synapsin family and the underlying molecular mechanisms that contribute to several neurological disorders.These physiologically important roles of synapsins associated with neurological disorders are just beginning to be understood. A detailed understanding of the diversified expression of synapsins may serve to strategize novel therapeutic approaches for these debilitating neurological disorders.
基金supported by the National Natural Science Foundation of China,No.81673719,81173175 and 81303074a grant from China Postdoctoral Science Foundation,No.2016M600639 and 2017T100614
文摘Xuefu Zhuyu decoction has been used for treating traumatic brain injury and improving post-traumatic dysfunction, but its mechanism of action needs further investigation. This study established rat models of traumatic brain injury by controlled cortical impact. Rat models were intragastrically administered 9 and 18 g/kg Xuefu Zhuyu decoction once a day for 14 or 21 days. Changes in neurological function were assessed by modified neurological severity scores and the Morris water maze. Immunohistochemistry, western blot assay, and re- verse-transcription polymerase chain reaction were used to analyze synapsin protein and mRNA expression at the injury site of rats. Our results showed that Xuefu Zhuyu decoction visibly improved neurological function of rats with traumatic brain injury. These changes were accompanied by increased expression of synaptophysin, synapsin I, and postsynaptic density protein-95 protein and mRNA in a dose-de- pendent manner. These findings indicate that Xuefu Zhuyu decoction increases synapsin expression and improves neurological deficits alder traumatic brain injury.
基金funded by the Key Science and Technology Project of Shaanxi Provincial "13115"Technology Innovation Engineering,No.2010ZDKG-65
文摘The Xingnao Jieyu capsule has been shown to effectively relieve neurologic impairments and les- sen depression. It remains poorly understood whether this capsule can be used to treat post-stroke depression. Thus, in the present study, we established a rat model of post-stroke depression using left middle cerebral artery occlusions in combination of chronic unpredictable stress and solitary housing during development. Experimental rats received intragastric perfusion with 0.82, 0.41, and 0.20 g/kg Xingnao Jieyu capsules separately dissolved in 2 mL distilled water. Fluoxetine served as a positive control. The treatment was conducted over 28 days. Sugar water consumption test, open-field test, real-time fluorescent quantitative PCR and immunohistochemical staining results demonstrated that intragastric perfusion with various doses of Xingnao Jieyu capsules increased sugar water consumption, voluntary behaviors and synaptotagmin mRNA and protein expression in rats with post-stroke depression. These therapeutic effects were similar to those of fluoxetine. These results indicate that Xingnao Jieyu capsules upregulate synaptotagmin expression in hip pocampi of rats with post-stroke depression, and exert antidepressant effects.
基金supported by the National Natural Science Foundation of China,Nos.81974358,81772453(to DSX)。
文摘Paired associative stimulation has been used in stroke patients as an innovative recovery treatment.However,the mechanisms underlying the therapeutic effectiveness of paired associative stimulation on neurological function remain unclear.In this study,rats were randomly divided into middle cerebral occlusion model(MCAO)and paired associated magnetic stimulation(PAMS)groups.The MCAO rat model was produced by middle cerebral artery embolization.The PAMS group received PAMS on days 3 to 20 post MCAO.The MCAO group received sham stimulation,three times every week.Within 18 days after ischemia,rats were subjected to behavioral experiments—the foot-fault test,the balance beam walking test,and the ladder walking test.Balance ability was improved on days 15 and 17,and the footfault rate was less in their affected limb on day 15 in the PAMS group compared with the MCAO group.Western blot assay showed that the expression levels of brain derived neurotrophic factor,glutamate receptor 2/3,postsynaptic density protein 95 and synapsin-1 were significantly increased in the PAMS group compared with the MCAO group in the ipsilateral sensorimotor cortex on day 21.Resting-state functional magnetic resonance imaging revealed that regional brain activities in the sensorimotor cortex were increased in the ipsilateral hemisphere,but decreased in the contralateral hemisphere on day 20.By finite element simulation,the electric field distribution showed a higher intensity,of approximately 0.4 A/m^2,in the ischemic cortex compared with the contralateral cortex in the template.Together,our findings show that PAMS upregulates neuroplasticity-related proteins,increases regional brain activity,and promotes functional recovery in the affected sensorimotor cortex in the rat MCAO model.The experiments were approved by the Institutional Animal Care and Use Committee of Fudan University,China(approval No.201802173 S)on March 3,2018.
基金supported by the Key Laboratory of Brain Disease Bioinformation of Jiangsu Province of China,No.Jsbl1202
文摘Dendrite ramification affects synaptic strength and plays a crucial role in memory. Previous studies revealed a correlation between beta 2-adrenergic receptor dysfunction and Alzheimer＇s disease （AD）, although the mechanism involved is still poorly understood. The current study investigated the potential effect of the selective β2-adrenergic receptor antagonist, ICI 118551 （ICI）, on Aβ deposits and AD-related cognitive impairment. Morris water maze test results demonstrated that the performance of AD-transgenic （TG） mice treated with ICI （AD-TG/ICI） was significantly poorer compared with NaCl-treated AD-TG mice （AD-TG/NaCl）, suggesting that β2-adrenergic receptor blockage by ICI might reduce the learning and memory abilities of mice. Golgi staining and immunohistochemical staining revealed that blockage of the β2-adrenergic receptor by ICI treatment decreased the number of dendritic branches, and ICI treatment in AD-TG mice decreased the expression of hippocampal synaptophysin and synapsin 1. Western blot assay results showed that the blockage of β2-adrener- gic receptor increased amyloid-β accumulation by downregulating hippocampal a-secretase activity and increasing the phosphorylation of amyloid precursor protein. These findings suggest that blocking the β2-adrenergic receptor inhibits dendrite ramification of hippocampal neurons in a mouse model of AD.
基金supported by the National Natural Science Foundation of China(grant number 81273110)the Health Industry Research Special Funds for public welfare projects(grant number 201402021)the National Key Technology Research and Development Program(grant number 2014BAI12B02)
文摘Objective To investigate acrylamide （ACR）-induced subacute neurotoxic effects on the central nervous system （CNS） at the synapse level in rats. Methods Thirty-six Sprague Dawley （SD） rats were randomized into three groups, （1） a 30 mg/kg ACR-treated group, （2） a 50 mg/kg ACR-treated group, and （3） a normal saline （NS）-treated control group. Body weight and neurological changes were recorded each day. At the end of the test, cerebral cortex and cerebellum tissues were harvested and viewed using light and electron microscopy. Additionally, the expression of Synapsin I and P-Synapsin I in the cerebral cortex and cerebellum were investigated. Results The 50 mg/kg ACR-treated rats showed a significant reduction in body weight compared with untreated individuals （P 〈 0.05）. Rats exposed to ACR showed a significant increase in gait scores compared with the NS control group （P 〈 0.05）. Histological examination indicated neuronal structural damage in the 50 mg/kg ACR treatment group. The active zone distance （AZD） and the nearest neighbor distance （NND） of synaptic vesicles in the cerebral cortex and cerebellum were increased in both the 30 mg/kg and 50 mg/kg ACR treatment groups. The ratio of the distribution of synaptic vesicles in the readily releasable pool （RRP） was decreased. Furthermore, the expression levels of Synapsin I and P-Synapsin I in the cerebral cortex and cerebellum were decreased in both the 30 mg/kg and 50 mg/kg ACR treatment groups. Conclusion Subacute ACR exposure contributes to neuropathy in the rat CNS. Functional damage of synaptic proteins and vesicles may be a mechanism of ACR neurotoxicity.
基金supported by the National Natural Science Foundation of China,No.81601121,31500968the Natural Science Foundation of Jiangsu Province of China,No.BK20150163the Fundamental Research Fund for the Central Universities of China,No.JUSRP11567
文摘Impaired hippocampal neurogenesis is one of the early pathological features of Alzheimer＇s disease. Enhancing adult hippocampal neuro- genesis has been pursued as a potential therapeutic strategy for Alzheimer＇s disease. Recent studies have demonstrated that environmental novelty activates β2-adrenergic signaling and prevents the memory impairment induced by amyloid-β oligomers. Here, we hypothesized that β2-adrenoceptor activation would enhance neurogenesis and ameliorate memory deficits in Alzheimer＇s disease. To test this hypothe- sis, we investigated the effects and mechanisms of action of β2-adrenoceptor activation on neurogenesis and memory in amyloid precursor protein/presenilin 1 （APP/PS1） mice using the agonist clenbuterol （intraperitoneal injection, 2 mg/kg）. We found that β2-adrenoceptor ac- tivation enhanced hippocampal neurogenesis, ameliorated memory deficits, and increased dendritic branching and the density of dendritic spines, lhese effects were associated with the upregulation of postsynaptic density 95, synapsin 1 and synaptophysin in APP/PS1 mice. Furthermore, β2-adrenoceptor activation decreased cerebral amyloid plaques by decreasing APP phosphorylation at Thr668. These findings suggest that β2-adrenoceptor activation enhances neurogenesis and ameliorates memory deficits in APP/PS 1 mice.
文摘Brain-derived neurotrophic factor （BDNF） promotes synaptic formation and functional maturation by upregulating synapsin expression in cortical and hippocampal neurons. However, it remains controversial whether BDNF affects synapsin expression in spinal cord anterior horn neurons. Wistar rat spinal cord anterior horn neurons were cultured in serum-supplemented medium containing BDNF, BDNF antibody, and Hank＇s solution for 3 days, and then synapsin I and synaptophysin protein and mRNA expression was detected. Under serum-supplemented conditions the number of surviving neurons in the spinal cord anterior horn was similar among BDNF, anti-BDNF, and control groups （P 〉 0.05）. Synapsin I and synaptophysin protein and mRNA expressions were increased in BDNF-treated neurons, but decreased in BDNF antibody-treated neurons （P 〈 0.01）. These results indicated that BDNF significantly promotes synapsin I and synaptophysin expression in in vitro-cultured rat spinal cord anterior horn neurons.
