The clinical effect of electroacupuncture on depression is widely recognized. However, the signal transduction pathways and target proteins involved remain unclear. In the present study, rat models of chronic restrain...The clinical effect of electroacupuncture on depression is widely recognized. However, the signal transduction pathways and target proteins involved remain unclear. In the present study, rat models of chronic restraint stress were used to explore the mechanism by which electroacupuncture alleviates depression. Rats were randomly divided into control, model, and electroacupuncture groups. Chronic restraint stress was induced in the model and electroacupuncture groups by restraining rats for 28 days. In the electroacupuncture group, electroacupuncture pretreatment at Baihui(GV20) and Yintang(GV29) acupoints was performed daily(1 m A, 2 Hz, discontinuous wave, 20 minutes) prior to restraint for 28 days. Open field tests and body weight measurements were carried out to evaluate the depressive symptoms at specific time points. On day 28, the crossing number, rearing number, and body weights of the model group were significantly lower than those in the control group. Behavior test results indicated that rat models of depressive-like symptoms were successfully established by chronic restraint stress combined with solitary raising. On day 28, an isobaric tag for a relative and absolute quantitation-based quantitative proteomic approach was performed to identify differentially expressed proteins in hippocampal samples obtained from the model and electroacupuncture groups. The potential function of these differential proteins was predicted through the use of the Cluster of Orthologous Groups of proteins(COG) database. Twenty-seven differential proteins(uncharacteristic proteins expected) were selected from the model and electroacupuncture groups. In addition to unknown protein functions, COG are mainly concentrated in general prediction function, mechanism of signal transduction, amino acid transport and metabolism groups. This suggests that electroacupuncture improved depressive-like symptoms by regulating differential proteins, and most of these related proteins exist in nerve cells.展开更多
Objective To investigate the ameliorating effect of ginsenoside Rg1 on the depression-like behaviors induced by chronic restraint stress(CRS)in rats and the underlying mechanisms.Methods Forty male Wistar rats were di...Objective To investigate the ameliorating effect of ginsenoside Rg1 on the depression-like behaviors induced by chronic restraint stress(CRS)in rats and the underlying mechanisms.Methods Forty male Wistar rats were divided into 4 groups according to their baseline sucrose preference:control group,model group,and Rg1-treated groups(5 and 10 mg/kg).Except for control group,the groups were exposed to CRS(6 h/day)for 28 days.All drugs were intraperitoneally administered once daily to CRS rats after restraint stress for 14 days.The behavioral tests were carried out via the open field test(OFT),sucrose preference test(SPT),forced swim test(FST),and the Morris water maze(MWM)4 weeks following CRS induction.The levels of serum corticosterone(CORT)and the activities of the antioxidant defense biomarkers(SOD,MDA and GSH-x)in the prefrontal cortex(PFC)were analyzed using commercial ELISA kits.The levels of the neurotransmitter(5-HT,5-HIAA,Ach,NE,GABA and Glu)in the PFC were measured by ultra-performance liquid chromatography tandem mass spectrometry.The protein expression of BDNF,Trkb,Bax and Bcl-2 in the PFC was detected by western blotting.Results Owing to increased sucrose consumption in the SPT,decreased immobility time in the FST,and the improved cognitive performance in MWM,chronic treatment with Ginsenoside Rg1 was found to significantly attenuate depressionlike behaviors(anhedonia,behavioral despair and poor spatial memory)in rats.Moreover,CRS exposure caused evident alterations in the levels of the neurotransmitters(5-HT,5-HIAA,Ach,GABA and Glu)and the activities of the antioxidant defense biomarkers(SOD,MDA and GSH-x)in the PFC and the levels of corticosterone in serum.However,Ginsenoside Rg1 treatment could restore these levels to normal values.Additionally,Ginsenoside Rg1 treatment significantly reverted the decreased expression of BDNF,Trkb and Bcl-2 and the increased expression of Bax in the PFC of CRS rats.Conclusions Ginsenoside Rg1 could attenuate the CRS-induced depression-like behaviors,in part,by regulating neurotransmitter levels and HPA function,antagonizing oxidative stress and apoptosis,and restoring BDNF-TrkB signaling in PFC.Altogether,our results provide a novel basis regarding the potential therapeutic effects of Rg1 on depression.展开更多
Objective To investigate the roles of estrogen and kalirin-7 in chronic restraint stress (CRS)-induced depression and the pathophysiological mechanism of depression. Methods Healthy female mice from Institute of Can...Objective To investigate the roles of estrogen and kalirin-7 in chronic restraint stress (CRS)-induced depression and the pathophysiological mechanism of depression. Methods Healthy female mice from Institute of Cancer Research (ICR) were randomly divided into 3 groups: control group, CRS group, and estrogen + CRS group. CRS was used to establish the animal model of depression. Forced swimming test and immunohistochemistry method were utilized to investigate the animal behavior and kalirin-7 expression in the hippocampus, respectively. Results Compared with the control group, the CRS mice displayed depression-like behaviors, including a significant reduction in body weight, a significant increase in immobility time in forced swimming test, and a dramatic decrease in kalirin-7 expression in the hippocampus. However, administration of estrogen attenuated the CRS-induced negative behaviors, and simultaneously increased kalirin-7 expression. Conclusion Estrogen replacement therapy (ERT) could prevent CRS-induced depression-like behaviors in female ICR mice. Besides, kalirin-7 also plays a role in preventing CRS-induced depression-like behaviors.展开更多
The depressant-like effects of albiflorin(AF) were studied on stressed chronic restraint stress(CRS) rats. Experimental rats were subjected to immobilization stress for a daily 6 h-restraining in a plastic restrainer ...The depressant-like effects of albiflorin(AF) were studied on stressed chronic restraint stress(CRS) rats. Experimental rats were subjected to immobilization stress for a daily 6 h-restraining in a plastic restrainer for continuous 21 d and were treated with 30 or 15 mg·kg-1 of AF for 21 d. Control rats were maintained in completely non stressed conditions. Behavioral tests and biochemical analysis were applied to investigating a regulatory mechanism of anti-stress of AF. Treatment with AF significantly restored the depressant-like behaviors. Besides, AF increased the levels of 5-hydroxytryptophan(5-HT), 5-hydroxyindoleacetic acid(5-HIAA),noradrenaline(NE) and dopamine(DA) in the hippocampus and increased the level of brain-derived neurotrophic factor(BDNF) in serum and protein expression in hippocampus. In addition, AF decreased the levels of hypothalamo-pituitary-adrenal(HPA) cascade,reduced the level of NO and c GMP in serum and inhibited the overexpression of 5-HT2AR m RNA and protein expression. Taken together, AF can modulate the NO-mediated network pathway in the hippocampus against stress-induced depressive-like behaviors.These physiological and behavioral changes allow rats to avoid potential deleterious effects of stress that may result from chronically elevated levels of glucocorticosteroids over days.展开更多
Objective: To analyze the proteomic characteristics of Gan (肝))--ssttaaggnnaannccyy syndrome ((GGSSSS)) by seeking the differential protein in blood and tissues of GSS model rats.Methods: GSS model rats were...Objective: To analyze the proteomic characteristics of Gan (肝))--ssttaaggnnaannccyy syndrome ((GGSSSS)) by seeking the differential protein in blood and tissues of GSS model rats.Methods: GSS model rats were established by chronic restraint stress,keeping rats in restrain chamber for 6 h every day for 21 successive days.Their blood and liver samples were collected at the end of experiment for differential protein detection with methods of isoelectrofocusing and polyacrylamide SDS-PAGE,silver staining,and scanning.The gel images were analyzed with Imagemaster 2D Elite software,and the excavated differential protein spots were identified with matrix assistant laser resolving TOF mass spectrometry,Western blot,ELISA,and RT-PCR,respectively.Results: A method for isolating the protein in blood serum and tissues by two-dimensional gel electrophoresis was established and optimized.Six serum proteins and three liver proteins that differentially expressed were identified.The down-regulated differential proteins in serum of GSS model rats were serum albumin precursor,beta 1 globin,antibody against muscle acetylcholine receptor,Ig lambda-2 C region,and transthyretin (TTR),and those in liver tissue were aryl sulfotransferase,enoyl-CoA hydratase,and TTR.TTR down-regulation was found in both serum and liver.Preliminary biological information analysis showed that these differential proteins involved in immune,neuroendocrine,nutrition,and substance metabolism.Conclusion: Proteomic analysis of differential proteins showed that TTR,aryl sulfotransferase,and enoyl-CoA hydratase expressions are downregulated in the GSS model rats,suggesting that the susceptibility of cancer could be enhanced by chronic stress.展开更多
基金supported by the National Natural Science Foundation of China,No.81373729
文摘The clinical effect of electroacupuncture on depression is widely recognized. However, the signal transduction pathways and target proteins involved remain unclear. In the present study, rat models of chronic restraint stress were used to explore the mechanism by which electroacupuncture alleviates depression. Rats were randomly divided into control, model, and electroacupuncture groups. Chronic restraint stress was induced in the model and electroacupuncture groups by restraining rats for 28 days. In the electroacupuncture group, electroacupuncture pretreatment at Baihui(GV20) and Yintang(GV29) acupoints was performed daily(1 m A, 2 Hz, discontinuous wave, 20 minutes) prior to restraint for 28 days. Open field tests and body weight measurements were carried out to evaluate the depressive symptoms at specific time points. On day 28, the crossing number, rearing number, and body weights of the model group were significantly lower than those in the control group. Behavior test results indicated that rat models of depressive-like symptoms were successfully established by chronic restraint stress combined with solitary raising. On day 28, an isobaric tag for a relative and absolute quantitation-based quantitative proteomic approach was performed to identify differentially expressed proteins in hippocampal samples obtained from the model and electroacupuncture groups. The potential function of these differential proteins was predicted through the use of the Cluster of Orthologous Groups of proteins(COG) database. Twenty-seven differential proteins(uncharacteristic proteins expected) were selected from the model and electroacupuncture groups. In addition to unknown protein functions, COG are mainly concentrated in general prediction function, mechanism of signal transduction, amino acid transport and metabolism groups. This suggests that electroacupuncture improved depressive-like symptoms by regulating differential proteins, and most of these related proteins exist in nerve cells.
基金funding support from the Open Funding Project of National Key Laboratory of Human Factors Engineering (No. SYFD150051808K)the National Key Research and Development Program of China (No. 2016YFE0131800)the Highend Talents Recruitments Program (Liu Xin-Min group) of Luzhou Municipal People’s Government and Development of Animal Model on Human Diseases (No. 2016-I2M-2-006)
文摘Objective To investigate the ameliorating effect of ginsenoside Rg1 on the depression-like behaviors induced by chronic restraint stress(CRS)in rats and the underlying mechanisms.Methods Forty male Wistar rats were divided into 4 groups according to their baseline sucrose preference:control group,model group,and Rg1-treated groups(5 and 10 mg/kg).Except for control group,the groups were exposed to CRS(6 h/day)for 28 days.All drugs were intraperitoneally administered once daily to CRS rats after restraint stress for 14 days.The behavioral tests were carried out via the open field test(OFT),sucrose preference test(SPT),forced swim test(FST),and the Morris water maze(MWM)4 weeks following CRS induction.The levels of serum corticosterone(CORT)and the activities of the antioxidant defense biomarkers(SOD,MDA and GSH-x)in the prefrontal cortex(PFC)were analyzed using commercial ELISA kits.The levels of the neurotransmitter(5-HT,5-HIAA,Ach,NE,GABA and Glu)in the PFC were measured by ultra-performance liquid chromatography tandem mass spectrometry.The protein expression of BDNF,Trkb,Bax and Bcl-2 in the PFC was detected by western blotting.Results Owing to increased sucrose consumption in the SPT,decreased immobility time in the FST,and the improved cognitive performance in MWM,chronic treatment with Ginsenoside Rg1 was found to significantly attenuate depressionlike behaviors(anhedonia,behavioral despair and poor spatial memory)in rats.Moreover,CRS exposure caused evident alterations in the levels of the neurotransmitters(5-HT,5-HIAA,Ach,GABA and Glu)and the activities of the antioxidant defense biomarkers(SOD,MDA and GSH-x)in the PFC and the levels of corticosterone in serum.However,Ginsenoside Rg1 treatment could restore these levels to normal values.Additionally,Ginsenoside Rg1 treatment significantly reverted the decreased expression of BDNF,Trkb and Bcl-2 and the increased expression of Bax in the PFC of CRS rats.Conclusions Ginsenoside Rg1 could attenuate the CRS-induced depression-like behaviors,in part,by regulating neurotransmitter levels and HPA function,antagonizing oxidative stress and apoptosis,and restoring BDNF-TrkB signaling in PFC.Altogether,our results provide a novel basis regarding the potential therapeutic effects of Rg1 on depression.
基金supported by the Natural Science Foundation of Shaanxi Province, China (No.2006C240)
文摘Objective To investigate the roles of estrogen and kalirin-7 in chronic restraint stress (CRS)-induced depression and the pathophysiological mechanism of depression. Methods Healthy female mice from Institute of Cancer Research (ICR) were randomly divided into 3 groups: control group, CRS group, and estrogen + CRS group. CRS was used to establish the animal model of depression. Forced swimming test and immunohistochemistry method were utilized to investigate the animal behavior and kalirin-7 expression in the hippocampus, respectively. Results Compared with the control group, the CRS mice displayed depression-like behaviors, including a significant reduction in body weight, a significant increase in immobility time in forced swimming test, and a dramatic decrease in kalirin-7 expression in the hippocampus. However, administration of estrogen attenuated the CRS-induced negative behaviors, and simultaneously increased kalirin-7 expression. Conclusion Estrogen replacement therapy (ERT) could prevent CRS-induced depression-like behaviors in female ICR mice. Besides, kalirin-7 also plays a role in preventing CRS-induced depression-like behaviors.
基金supported by the National Nature Science Foundation of China (Nos. 81473370 and 81173569)。
文摘The depressant-like effects of albiflorin(AF) were studied on stressed chronic restraint stress(CRS) rats. Experimental rats were subjected to immobilization stress for a daily 6 h-restraining in a plastic restrainer for continuous 21 d and were treated with 30 or 15 mg·kg-1 of AF for 21 d. Control rats were maintained in completely non stressed conditions. Behavioral tests and biochemical analysis were applied to investigating a regulatory mechanism of anti-stress of AF. Treatment with AF significantly restored the depressant-like behaviors. Besides, AF increased the levels of 5-hydroxytryptophan(5-HT), 5-hydroxyindoleacetic acid(5-HIAA),noradrenaline(NE) and dopamine(DA) in the hippocampus and increased the level of brain-derived neurotrophic factor(BDNF) in serum and protein expression in hippocampus. In addition, AF decreased the levels of hypothalamo-pituitary-adrenal(HPA) cascade,reduced the level of NO and c GMP in serum and inhibited the overexpression of 5-HT2AR m RNA and protein expression. Taken together, AF can modulate the NO-mediated network pathway in the hippocampus against stress-induced depressive-like behaviors.These physiological and behavioral changes allow rats to avoid potential deleterious effects of stress that may result from chronically elevated levels of glucocorticosteroids over days.
基金Supported by the National Natural Science Foundation of China(No.30371713,30672769)
文摘Objective: To analyze the proteomic characteristics of Gan (肝))--ssttaaggnnaannccyy syndrome ((GGSSSS)) by seeking the differential protein in blood and tissues of GSS model rats.Methods: GSS model rats were established by chronic restraint stress,keeping rats in restrain chamber for 6 h every day for 21 successive days.Their blood and liver samples were collected at the end of experiment for differential protein detection with methods of isoelectrofocusing and polyacrylamide SDS-PAGE,silver staining,and scanning.The gel images were analyzed with Imagemaster 2D Elite software,and the excavated differential protein spots were identified with matrix assistant laser resolving TOF mass spectrometry,Western blot,ELISA,and RT-PCR,respectively.Results: A method for isolating the protein in blood serum and tissues by two-dimensional gel electrophoresis was established and optimized.Six serum proteins and three liver proteins that differentially expressed were identified.The down-regulated differential proteins in serum of GSS model rats were serum albumin precursor,beta 1 globin,antibody against muscle acetylcholine receptor,Ig lambda-2 C region,and transthyretin (TTR),and those in liver tissue were aryl sulfotransferase,enoyl-CoA hydratase,and TTR.TTR down-regulation was found in both serum and liver.Preliminary biological information analysis showed that these differential proteins involved in immune,neuroendocrine,nutrition,and substance metabolism.Conclusion: Proteomic analysis of differential proteins showed that TTR,aryl sulfotransferase,and enoyl-CoA hydratase expressions are downregulated in the GSS model rats,suggesting that the susceptibility of cancer could be enhanced by chronic stress.