Objective Postsynaptic density protein 95 （PSD-95） plays important roles in the regulation of glutamate signaling, such as that of N-methyl-D-aspartate receptors （NMDARs）. In this study, the functional roles of PS...Objective Postsynaptic density protein 95 （PSD-95） plays important roles in the regulation of glutamate signaling, such as that of N-methyl-D-aspartate receptors （NMDARs）. In this study, the functional roles of PSD-95 in tyrosine phosphorylafion of NMDAR subunit 2A （NR2A） and in apoptosis-like cell death induced by oxygen-glucose de- privation （OGD） in cultured rat cortical neurons were investigated. Methods We used immunoprecipitation and immuno- blotting to detect PSD-95 protein level, tyrosine phosphorylation level of NR2A, and the interaction between PSD-95 and NR2A or Src. Apoptosis-like cells were observed by 4,6-diamidino-2-phenylindole staining. Results Tyrosine phospho- rylation of NR2A and apoptosis-like cell death were increased after recovery following 60-min OGD. The increases were attenuated by pretreatment with antisense oligonucleotides against PSD-95 before OGD, but not by missense oligonucle- otides or vehicle. PSD-95 antisense oligonucleotides also inhibited the increased interaction between PSD-95 and NR2A or Src, while NR2A expression did not change under this condition. Conclusion PSD-95 may be involved in regulating NR2A tyrosine phosphorylation by Src kinase. Inhibition of PSD-95 expression can be neuroprotective against apoptosis- like cell death after recovery from OGD.展开更多
Bushen Tiansui decoction is composed of six traditional Chinese medicines：Herba Epimedii,Radix Polygoni multiflori,Plastrum testudinis,Fossilia Ossis Mastodi,Radix Polygalae,and Rhizoma Acorus tatarinowii.Because Bus...Bushen Tiansui decoction is composed of six traditional Chinese medicines：Herba Epimedii,Radix Polygoni multiflori,Plastrum testudinis,Fossilia Ossis Mastodi,Radix Polygalae,and Rhizoma Acorus tatarinowii.Because Bushen Tiansui decoction is effective against amyloid beta（Aβ） toxicity,we hypothesized that it would reduce hippocampal synaptic damage and improve cognitive function in Alzheimer＇s disease.To test this hypothesis,we used a previously established animal model of Alzheimer＇s disease,that is,microinjection of aggregated Aβ25–35 into the bilateral brain ventricles of Sprague-Dawley rats.We found that long-term（28 days） oral administration of Bushen Tiansui decoction（0.563,1.688,and 3.375 g/m L;4 m L/day） prevented synaptic loss in the hippocampus and increased the expression levels of synaptic proteins,including postsynaptic density protein 95,the N-methyl-D-aspartate receptor 2 B subunit,and Shank1.These results suggested that Bushen Tiansui decoction can protect synapses by maintaining the expression of these synaptic proteins.Bushen Tiansui decoction also ameliorated measures reflecting spatial learning and memory deficits that were observed in the Morris water maze（i.e.,increased the number of platform crossings and the amount of time spent in the target quadrant and decreased escape latency） following intraventricular injections of aggregated Aβ25–35 compared with those measures in untreated Aβ_（25–35）-injected rats.Overall,these results provided evidence that further studies on the prevention and treatment of dementia with this traditional Chinese medicine are warranted.展开更多
基金supported by the National Natural Science Foundation of China (30170220)Xuzhou Science and Technology Bureau of China (XZZD1157)+1 种基金Xuzhou Medical College (2011KJZ03)A Project Funded by the Priority Academic Program Development of Jingsu Higher Education Institutions
文摘Objective Postsynaptic density protein 95 （PSD-95） plays important roles in the regulation of glutamate signaling, such as that of N-methyl-D-aspartate receptors （NMDARs）. In this study, the functional roles of PSD-95 in tyrosine phosphorylafion of NMDAR subunit 2A （NR2A） and in apoptosis-like cell death induced by oxygen-glucose de- privation （OGD） in cultured rat cortical neurons were investigated. Methods We used immunoprecipitation and immuno- blotting to detect PSD-95 protein level, tyrosine phosphorylation level of NR2A, and the interaction between PSD-95 and NR2A or Src. Apoptosis-like cells were observed by 4,6-diamidino-2-phenylindole staining. Results Tyrosine phospho- rylation of NR2A and apoptosis-like cell death were increased after recovery following 60-min OGD. The increases were attenuated by pretreatment with antisense oligonucleotides against PSD-95 before OGD, but not by missense oligonucle- otides or vehicle. PSD-95 antisense oligonucleotides also inhibited the increased interaction between PSD-95 and NR2A or Src, while NR2A expression did not change under this condition. Conclusion PSD-95 may be involved in regulating NR2A tyrosine phosphorylation by Src kinase. Inhibition of PSD-95 expression can be neuroprotective against apoptosis- like cell death after recovery from OGD.
基金supported by the National Natural Science Foundation of China,No.81373705the Natural Science Foundation of Hunan Province in China,No.13JJ3030
文摘Bushen Tiansui decoction is composed of six traditional Chinese medicines：Herba Epimedii,Radix Polygoni multiflori,Plastrum testudinis,Fossilia Ossis Mastodi,Radix Polygalae,and Rhizoma Acorus tatarinowii.Because Bushen Tiansui decoction is effective against amyloid beta（Aβ） toxicity,we hypothesized that it would reduce hippocampal synaptic damage and improve cognitive function in Alzheimer＇s disease.To test this hypothesis,we used a previously established animal model of Alzheimer＇s disease,that is,microinjection of aggregated Aβ25–35 into the bilateral brain ventricles of Sprague-Dawley rats.We found that long-term（28 days） oral administration of Bushen Tiansui decoction（0.563,1.688,and 3.375 g/m L;4 m L/day） prevented synaptic loss in the hippocampus and increased the expression levels of synaptic proteins,including postsynaptic density protein 95,the N-methyl-D-aspartate receptor 2 B subunit,and Shank1.These results suggested that Bushen Tiansui decoction can protect synapses by maintaining the expression of these synaptic proteins.Bushen Tiansui decoction also ameliorated measures reflecting spatial learning and memory deficits that were observed in the Morris water maze（i.e.,increased the number of platform crossings and the amount of time spent in the target quadrant and decreased escape latency） following intraventricular injections of aggregated Aβ25–35 compared with those measures in untreated Aβ_（25–35）-injected rats.Overall,these results provided evidence that further studies on the prevention and treatment of dementia with this traditional Chinese medicine are warranted.
