In our previous studies,we have shown that(D-Ser2)oxyntomodulin(Oxm),a glucagon-like peptide 1(GLP-1)receptor(GLP1R)/glucagon receptor(GCGR)dual agonist peptide,protects hippocampal neurons against Aβ1-42-induced cyt...In our previous studies,we have shown that(D-Ser2)oxyntomodulin(Oxm),a glucagon-like peptide 1(GLP-1)receptor(GLP1R)/glucagon receptor(GCGR)dual agonist peptide,protects hippocampal neurons against Aβ1-42-induced cytotoxicity,and stabilizes the calcium homeostasis and mitochondrial membrane potential of hippocampal neurons.Additionally,we have demonstrated that(D-Ser2)Oxm improves cognitive decline and reduces the deposition of amyloid-beta in Alzheimer’s disease model mice.However,the protective mechanism remains unclear.In this study,we showed that 2 weeks of intraperitoneal administration of(D-Ser2)Oxm ameliorated the working memory and fear memory impairments of 9-month-old 3×Tg Alzheimer’s disease model mice.In addition,electrophysiological data recorded by a wireless multichannel neural recording system implanted in the hippocampal CA1 region showed that(D-Ser2)Oxm increased the power of the theta rhythm.In addition,(D-Ser2)Oxm treatment greatly increased the expression level of synaptic-associated proteins SYP and PSD-95 and increased the number of dendritic spines in 3×Tg Alzheimer’s disease model mice.These findings suggest that(D-Ser2)Oxm improves the cognitive function of Alzheimer’s disease transgenic mice by recovering hippocampal synaptic function and theta rhythm.展开更多
Objective :To observe the effect of electroacupuncture at pericardium meridian on neurological deficit, D-serine ( D-Ser ) content and NMDAR expression in ischemic brain tissue of rats with middle cerebral artery occl...Objective :To observe the effect of electroacupuncture at pericardium meridian on neurological deficit, D-serine ( D-Ser ) content and NMDAR expression in ischemic brain tissue of rats with middle cerebral artery occlusion ( MCAO ). Methods:A total of 36 SD rats were randomly divided into normal group, sham operation group, model group, EA pericardium meridian group, model+D-Ser group,and EA pericardium meridian+D-Ser group. The MCAO model was prepared by Zea Longa method. The model+D-Ser group and the EA pericardium meridian+D-Ser group were given exogenous D-Ser reagent(160 mg/kg i.p.) 30 minutes after the success of the insertion of the suture. EA pericardium meridian group and EA pericardium meridian+D-Ser group were treated with electroacupuncture for 30 min on the next day. The remaining groups were only bound for 30 min.Behavioral evaluation was performed at 6 h after successful modeling and 2 d after intervention, and then the rats were sacrificed. The content of D-Ser in ischemic brain tissue was measured by liquid chromatography tandem mass spectrometry, and the protein expression of NR1, NR2A and NR2B was detected by Western Blot. Results : Before treatment, compared with the normal group and the sham operation group, the behavioral scores of each group increased after modeling (P<0.05 );Compared with the model group, the behavioral scores of the model+D-Ser group and the EA pericardium meridian+D-Ser group were increased (P<0.05).After treatment, compared with the model group, there was no significant difference in the EA pericardium meridian group (P>0.05),The behavioral scores of the model+D-Ser group and the EA pericardium meridian+D-Ser group were still increased (P<0.05);Compared with the model+D-Ser group, the behavioral score of the EA pericardium meridian+D-Ser group was not statistically significant (P>0.05).Comparison before and after treatment in the group,except for the normal group and the sham operation group, the behavioral scores of each group were slightly increased, and the difference was not statistically significant (P>0.05).Compared with the model group, the content of D-Ser and the protein expression of NR1, NR2A and NR2B in the brain tissue of the model+D-Ser group were significantly increased (P<0.05);The protein expression of NR1, NR2A and NR2B decreased in EA pericardium meridian group (P<0.05);Compared with the model+ D-Ser group, the D-Ser content and the protein expression of NR1, NR2A and NR2B in the EA pericardium meridian+D-Ser group were decreased (P<0.05). Conclusion : EA at pericardium meridian points can reduce the D-Ser content in brain tissue of rats with acute MCAO, regulate the decrease of NR1, NR2A and NR2B protein expression, inhibit the NMDA receptor activity, and play a neuroprotective role.展开更多
基金supported by the National Natural Science Foundation of China,No.31600865(to ZJW)“Sanjin Scholars”of Shanxi Province of China,No.[2016]7(to MNW)+5 种基金Shanxi Province Science Foundation for Excellent Young Scholars of China,No.201801D211005(to MNW)the Applied Basic Research Program of Shanxi Province of China,No.201901D111358(to GZY)the Doctoral Startup Research Fund of Shanxi Medical University of China,No.03201536(to GZY)the Doctoral Startup Research Fund of the First Hospital of Shanxi Medical University of China,No.YJ1507(to GZY)the National Undergraduate Innovation Program of China,No.201910114019(to JXW)the Undergraduate Innovation Program of Shanxi Province of China,No.2020189(to XRZ).
文摘In our previous studies,we have shown that(D-Ser2)oxyntomodulin(Oxm),a glucagon-like peptide 1(GLP-1)receptor(GLP1R)/glucagon receptor(GCGR)dual agonist peptide,protects hippocampal neurons against Aβ1-42-induced cytotoxicity,and stabilizes the calcium homeostasis and mitochondrial membrane potential of hippocampal neurons.Additionally,we have demonstrated that(D-Ser2)Oxm improves cognitive decline and reduces the deposition of amyloid-beta in Alzheimer’s disease model mice.However,the protective mechanism remains unclear.In this study,we showed that 2 weeks of intraperitoneal administration of(D-Ser2)Oxm ameliorated the working memory and fear memory impairments of 9-month-old 3×Tg Alzheimer’s disease model mice.In addition,electrophysiological data recorded by a wireless multichannel neural recording system implanted in the hippocampal CA1 region showed that(D-Ser2)Oxm increased the power of the theta rhythm.In addition,(D-Ser2)Oxm treatment greatly increased the expression level of synaptic-associated proteins SYP and PSD-95 and increased the number of dendritic spines in 3×Tg Alzheimer’s disease model mice.These findings suggest that(D-Ser2)Oxm improves the cognitive function of Alzheimer’s disease transgenic mice by recovering hippocampal synaptic function and theta rhythm.
基金National Natural Science Foundation of China (No.81774421)Natural Science Foundation of Hunan Province (No.2018JJ2306)Hunan Provincial General Project of Postgraduate Scientific Research Innovation (No.CX20200809)。
文摘Objective :To observe the effect of electroacupuncture at pericardium meridian on neurological deficit, D-serine ( D-Ser ) content and NMDAR expression in ischemic brain tissue of rats with middle cerebral artery occlusion ( MCAO ). Methods:A total of 36 SD rats were randomly divided into normal group, sham operation group, model group, EA pericardium meridian group, model+D-Ser group,and EA pericardium meridian+D-Ser group. The MCAO model was prepared by Zea Longa method. The model+D-Ser group and the EA pericardium meridian+D-Ser group were given exogenous D-Ser reagent(160 mg/kg i.p.) 30 minutes after the success of the insertion of the suture. EA pericardium meridian group and EA pericardium meridian+D-Ser group were treated with electroacupuncture for 30 min on the next day. The remaining groups were only bound for 30 min.Behavioral evaluation was performed at 6 h after successful modeling and 2 d after intervention, and then the rats were sacrificed. The content of D-Ser in ischemic brain tissue was measured by liquid chromatography tandem mass spectrometry, and the protein expression of NR1, NR2A and NR2B was detected by Western Blot. Results : Before treatment, compared with the normal group and the sham operation group, the behavioral scores of each group increased after modeling (P<0.05 );Compared with the model group, the behavioral scores of the model+D-Ser group and the EA pericardium meridian+D-Ser group were increased (P<0.05).After treatment, compared with the model group, there was no significant difference in the EA pericardium meridian group (P>0.05),The behavioral scores of the model+D-Ser group and the EA pericardium meridian+D-Ser group were still increased (P<0.05);Compared with the model+D-Ser group, the behavioral score of the EA pericardium meridian+D-Ser group was not statistically significant (P>0.05).Comparison before and after treatment in the group,except for the normal group and the sham operation group, the behavioral scores of each group were slightly increased, and the difference was not statistically significant (P>0.05).Compared with the model group, the content of D-Ser and the protein expression of NR1, NR2A and NR2B in the brain tissue of the model+D-Ser group were significantly increased (P<0.05);The protein expression of NR1, NR2A and NR2B decreased in EA pericardium meridian group (P<0.05);Compared with the model+ D-Ser group, the D-Ser content and the protein expression of NR1, NR2A and NR2B in the EA pericardium meridian+D-Ser group were decreased (P<0.05). Conclusion : EA at pericardium meridian points can reduce the D-Ser content in brain tissue of rats with acute MCAO, regulate the decrease of NR1, NR2A and NR2B protein expression, inhibit the NMDA receptor activity, and play a neuroprotective role.
基金supported by the National Natural Science Foundation of China(No.31471080,31271201)the College Science and Technology Innovation Foundation of Shanxi Province,China(No.2015153)