The depression-like behavior phenotype,neurogenesis in the dentate gyrus and miR-124 expression in the hippocampus are the focus of current research on the pathogenesis of depression and antidepressant therapy.The pre...The depression-like behavior phenotype,neurogenesis in the dentate gyrus and miR-124 expression in the hippocampus are the focus of current research on the pathogenesis of depression and antidepressant therapy.The present study aimed to clarify the dynamic changes of depression-like behavior,dentate gyrus neurogenesis and hippocampal miR-124 expression during depression induced by chronic stress to reveal pathological features at different stages of depression and to further provide insight into depression treatment.Chronic unpredictable mild stress depression models were established by exposing Sprague-Dawley rats to various mild stressors,including white noise,thermal swimming,stroboscopic illumination,soiled cages,pairing with three other stressed animals,cold swimming,tail pinch,restraint and water and food deprivation.Chronic unpredictable mild stress model rats underwent dynamic observation from 1 to 8 weeks and were compared with a control group(normal feeding without any stressors).To observe changes in the depression-like behavior phenotype during chronic unpredictable mild stress-induced depression,a sucrose preference test was used to evaluate the degree of anhedonia.An open-field test was used to evaluate locomotor activity and anxiety status.Compared with the control group,chronic unpredictable mild stress rats lost weight but did not have a depression-like behavioral phenotype at 1-4 weeks.Chronic unpredictable mild stress rats presented decreased sucrose preference and locomotor activity at 5-8 weeks.In addition,chronic unpredictable mild stress rats did not have significant anxiety-like behavior during 1-8 weeks of modeling.To observe neurogenesis dysfunctions and changes in neuronal number in the dentate gyrus during chronic unpredictable mild stress-induced depression,markers(DCX and DCX/BrdU)of neural proliferation and differentiation and the neuronal marker NeuN were assessed by immunofluorescence.Compared with the control group,neurogenesis and the neuronal number in the dentate gyrus did not change from 2 to 6 weeks;however,neural proliferation and differentiation in the dentate gyrus decreased,and the number of neurons decreased until the eighth week in the chronic unpredictable mild stress group.Real-time quantitative reverse transcription polymerase chain reaction assays and fluorescence in situ hybridization were used to measure the expression of hippocampal miR-124 during chronic unpredictable mild stress-induced depression.The results showed that the expression of hippocampal miR-124 was unchanged during the first 4 weeks but increased from 5 to 6 weeks and decreased from 7 to 8 weeks compared with the control group.These findings indicate that during chronic unpredictable mild stress-induced depression,the behavioral phenotype,miR-124 expression in the hippocampus,neurogenesis in the dentate gyrus and neuronal numbers showed dynamic changes,which suggested that various pathological changes occur at different stages of depression.All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Guangzhou University of Chinese Medicine of China in March 2015.展开更多
Icariin(ICA) has a significant capacity to protect against depression and hippocampal injury,but it cannot effectively cross the bloodbrain barrier and accumulate in the brain.Therefore,the mechanism by which ICA prot...Icariin(ICA) has a significant capacity to protect against depression and hippocampal injury,but it cannot effectively cross the bloodbrain barrier and accumulate in the brain.Therefore,the mechanism by which ICA protects against hippocampal injury in depression remains unclear.In this study,we performed proteomics analysis of cerebrospinal fluid to investigate the mechanism by which ICA prevents dysfunctional hippocampal neurogenesis in depression.A rat model of depression was established through exposure to chronic unpredictable mild stress for 6 weeks,after which 120 mg/kg ICA was administered subcutaneously every day.The results showed that ICA alleviated depressive symptoms,learning and memory dysfunction,dysfunctional neurogenesis,and neuronal loss in the dentate gyrus of rats with depression.Neural stem cells from rat embryonic hippocampi were cultured in media containing 20% cerebrospinal fluid from each group of rats and then treated with 100 μM corticosterone.The addition of cerebrospinal fluid from rats treated with ICA largely prevented the corticosterone-mediated inhibition of neuronal proliferation and differentiation.Fifty-two differentially expressed proteins regulated by chronic unpredictable mild stress and ICA were identified through proteomics analysis of cerebrospinal fluid.These proteins were mainly involved in the ribosome,PI3 K-Akt signaling,and interleukin-17 signaling pathways.Parallel reaction monitoring mass spectrometry showed that Rps4 x,Rps12,Rps14,Rps19,Hsp90 b1,and Hsp90 aa1 were up-regulated by chronic unpredictable mild stress and down-regulated by ICA.In contrast,Htr A1 was down-regulated by chronic unpredictable mild stress and up-regulated by ICA.These findings suggest that ICA can prevent depression and dysfunctional hippocampal neurogenesis through regulating the expression of certain proteins found in the cerebrospinal fluid.The study was approved by the Experimental Animal Ethics Committee of Guangzhou University of Chinese Medicine of China in March 2017.展开更多
The traditional Chinese medicine Jiaweisinisan has antidepressant effects,and can inhibit hypothalamus-pituitary-adrenal gland axis hyperactivity in stress-induced depression.In this study,rat hippocampal neural precu...The traditional Chinese medicine Jiaweisinisan has antidepressant effects,and can inhibit hypothalamus-pituitary-adrenal gland axis hyperactivity in stress-induced depression.In this study,rat hippocampal neural precursor cells were cultured in serum-free medium in vitro and a stress damage model was established with 120 IJM corticosterone.Cells were treated with 10%(v/v)Jiaweisinisan drug-containing serum and the corticosterone antagonist RU38486.Results of the 3-(4,5-dimethylthiazol-2-yl)-3,5-di-phenytetrazoliumromide assay showed that both Jiaweisinisan drug-containing serum and RU38486 promoted the proliferation of neural precursor cells after corticosterone exposure.Immunofluorescence detection showed that after Jiaweisinisan drug-containing serum and RU38486 treatment,the 5-bromo-2-deoxyuridine/terminal deoxynucleotidyl transferase dUTP nick end labeling ratio in hippocampal neural precursor cells significantly increased,and the apoptotic rates of glial cells reduced,and neuron-like cell differentiation from neural precursor cells significantly increased.Our experimental findings indicate that Jiaweisinisan promotes hippocampal neurogenesis after stress damage.展开更多
Quality evaluation is a bottleneck restricting the modernization and internationalization of Chinese materia medica (CMM). Due to characteristics of multi-component, multi-efficacy, multi-target, the existing quality ...Quality evaluation is a bottleneck restricting the modernization and internationalization of Chinese materia medica (CMM). Due to characteristics of multi-component, multi-efficacy, multi-target, the existing quality evaluation system still cannot fully meet quality control needs of CMM. Hence, the author put forward “Bio-characteristic profiling related to clinic, BPRC” academic concept, meanwhile, fully take the advantage of analysis method with clinical monitoring superiority or profiling characteristics, build up “BPRC” new technology platform, in order to realize “real-time, dynamic and full-range monitoring” new technologies of CMM quality evaluation system and promote the further development of CMM industry.展开更多
in hippocampal neurons is an important contributor to depression. [Ca^2＋]i of hippocampal neurons may raise rapidly with increased corticosterone concentrations, leading to apoptosis. The anti-depressant effects of X...in hippocampal neurons is an important contributor to depression. [Ca^2＋]i of hippocampal neurons may raise rapidly with increased corticosterone concentrations, leading to apoptosis. The anti-depressant effects of Xiaoyaosan （Free and Easy Wanderer＇s Powder） may inhibit apoptosis by down regulating the [Ca^2＋]i overload. PC12 cells were containing with corticosterone to simulate neuronal injury, dosed with Xiaoyaosan-containing serum, and the following parameters were measured： apoptosis,[Ca^2＋]i overload, and changes in mitochondrial membrane potential （△ψm） and bioenergetics. High-dose Xiaoyaosan-containing serum （the dose of intragastric administration was 2.633 g herb/mL） not only inhibited morphological injury and cell apoptosis, but also suppressed [Ca^2＋]i overload induced by corticosterone. Xiaoyaosan also blocked the decrease in mitochondrial membrane potential and adenosine triphosphate levels induced by corticosterone. Xiaoyaosan dose-dependently suppresses corticosterone-induced apoptosis, potentially via inhibiting [Ca^2＋]ioverload, and prevents impaired mitochondrial bioenergetics by maintaining mitochondrial membrane potential and adenosine triphosphate production, providing a putative mechanism for its antidepressant effects.展开更多
Background:As type 2 diabetes mellitus(T2DM)biomarkers,branched-chain amino acids(BCAAs:valine,leucine and isoleucine)and aromatic amino acids(AAAs:phenylalanine,tryptophan and tyrosine)may be correlated with the occu...Background:As type 2 diabetes mellitus(T2DM)biomarkers,branched-chain amino acids(BCAAs:valine,leucine and isoleucine)and aromatic amino acids(AAAs:phenylalanine,tryptophan and tyrosine)may be correlated with the occurrence and development of T2DM.However,there is still no consensus on the disperse and isolated biomarkers of T2DM.Purpose:To explore the correlation between amino acids and T2DM based on integrated biomarker approach revealed.Methods:PubMed,Web of Science and CNKI were selected to search the literature published until August 31,2019.The included studies described the association between BCAAs,AAAs and T2DM.Random effect model and fixed effect model were adopted in pooled analysis to determine mean difference and 95 percent confidence interval of metabolites.Integrated biomarker was constructed in form of concentration change ratios or risk ratio(RR),relative risk(HR)and odds ratio(OR)of BCAAs and AAAs to reflect the integrated change information of amino acids.Results:The selected 20 studies contained 14942 healthy individuals and 3615 T2DM patients.The levels of BCAAs,phenylalanine and tyrosine both in plasma and serum samples were increased among all T2DM patients compared with those of the healthy control subjects(P<0.00001).However,the mean difference of tryptophan concentration was not statistically significant(P=0.60).The concentration change ratios or HR/RR/OR of BCAAs and AAAs were connected to form integrated biomarker.Conclusion:The integrated biomarker including BCAAs and AAAs could reflect the basic characteristics of T2DM,which has the potential clinical value on comprehensive diagnosis of T2DM.展开更多
基金supported by the National Natural Science Foundation of China,No.81573858(to LLW)the Natural Science Foundation of Guangdong Province of China,No.2016A030313648(to CY)the Major Basic Research Project of Educational Commission of Guangdong Province of China,No.2017KZDXM020(to CY)
文摘The depression-like behavior phenotype,neurogenesis in the dentate gyrus and miR-124 expression in the hippocampus are the focus of current research on the pathogenesis of depression and antidepressant therapy.The present study aimed to clarify the dynamic changes of depression-like behavior,dentate gyrus neurogenesis and hippocampal miR-124 expression during depression induced by chronic stress to reveal pathological features at different stages of depression and to further provide insight into depression treatment.Chronic unpredictable mild stress depression models were established by exposing Sprague-Dawley rats to various mild stressors,including white noise,thermal swimming,stroboscopic illumination,soiled cages,pairing with three other stressed animals,cold swimming,tail pinch,restraint and water and food deprivation.Chronic unpredictable mild stress model rats underwent dynamic observation from 1 to 8 weeks and were compared with a control group(normal feeding without any stressors).To observe changes in the depression-like behavior phenotype during chronic unpredictable mild stress-induced depression,a sucrose preference test was used to evaluate the degree of anhedonia.An open-field test was used to evaluate locomotor activity and anxiety status.Compared with the control group,chronic unpredictable mild stress rats lost weight but did not have a depression-like behavioral phenotype at 1-4 weeks.Chronic unpredictable mild stress rats presented decreased sucrose preference and locomotor activity at 5-8 weeks.In addition,chronic unpredictable mild stress rats did not have significant anxiety-like behavior during 1-8 weeks of modeling.To observe neurogenesis dysfunctions and changes in neuronal number in the dentate gyrus during chronic unpredictable mild stress-induced depression,markers(DCX and DCX/BrdU)of neural proliferation and differentiation and the neuronal marker NeuN were assessed by immunofluorescence.Compared with the control group,neurogenesis and the neuronal number in the dentate gyrus did not change from 2 to 6 weeks;however,neural proliferation and differentiation in the dentate gyrus decreased,and the number of neurons decreased until the eighth week in the chronic unpredictable mild stress group.Real-time quantitative reverse transcription polymerase chain reaction assays and fluorescence in situ hybridization were used to measure the expression of hippocampal miR-124 during chronic unpredictable mild stress-induced depression.The results showed that the expression of hippocampal miR-124 was unchanged during the first 4 weeks but increased from 5 to 6 weeks and decreased from 7 to 8 weeks compared with the control group.These findings indicate that during chronic unpredictable mild stress-induced depression,the behavioral phenotype,miR-124 expression in the hippocampus,neurogenesis in the dentate gyrus and neuronal numbers showed dynamic changes,which suggested that various pathological changes occur at different stages of depression.All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Guangzhou University of Chinese Medicine of China in March 2015.
基金supported by the National Natural Science Foundation of China,No.81774102 (to LLW)。
文摘Icariin(ICA) has a significant capacity to protect against depression and hippocampal injury,but it cannot effectively cross the bloodbrain barrier and accumulate in the brain.Therefore,the mechanism by which ICA protects against hippocampal injury in depression remains unclear.In this study,we performed proteomics analysis of cerebrospinal fluid to investigate the mechanism by which ICA prevents dysfunctional hippocampal neurogenesis in depression.A rat model of depression was established through exposure to chronic unpredictable mild stress for 6 weeks,after which 120 mg/kg ICA was administered subcutaneously every day.The results showed that ICA alleviated depressive symptoms,learning and memory dysfunction,dysfunctional neurogenesis,and neuronal loss in the dentate gyrus of rats with depression.Neural stem cells from rat embryonic hippocampi were cultured in media containing 20% cerebrospinal fluid from each group of rats and then treated with 100 μM corticosterone.The addition of cerebrospinal fluid from rats treated with ICA largely prevented the corticosterone-mediated inhibition of neuronal proliferation and differentiation.Fifty-two differentially expressed proteins regulated by chronic unpredictable mild stress and ICA were identified through proteomics analysis of cerebrospinal fluid.These proteins were mainly involved in the ribosome,PI3 K-Akt signaling,and interleukin-17 signaling pathways.Parallel reaction monitoring mass spectrometry showed that Rps4 x,Rps12,Rps14,Rps19,Hsp90 b1,and Hsp90 aa1 were up-regulated by chronic unpredictable mild stress and down-regulated by ICA.In contrast,Htr A1 was down-regulated by chronic unpredictable mild stress and up-regulated by ICA.These findings suggest that ICA can prevent depression and dysfunctional hippocampal neurogenesis through regulating the expression of certain proteins found in the cerebrospinal fluid.The study was approved by the Experimental Animal Ethics Committee of Guangzhou University of Chinese Medicine of China in March 2017.
基金supported by the National NaturalScience Foundation of China,No.30500660
文摘The traditional Chinese medicine Jiaweisinisan has antidepressant effects,and can inhibit hypothalamus-pituitary-adrenal gland axis hyperactivity in stress-induced depression.In this study,rat hippocampal neural precursor cells were cultured in serum-free medium in vitro and a stress damage model was established with 120 IJM corticosterone.Cells were treated with 10%(v/v)Jiaweisinisan drug-containing serum and the corticosterone antagonist RU38486.Results of the 3-(4,5-dimethylthiazol-2-yl)-3,5-di-phenytetrazoliumromide assay showed that both Jiaweisinisan drug-containing serum and RU38486 promoted the proliferation of neural precursor cells after corticosterone exposure.Immunofluorescence detection showed that after Jiaweisinisan drug-containing serum and RU38486 treatment,the 5-bromo-2-deoxyuridine/terminal deoxynucleotidyl transferase dUTP nick end labeling ratio in hippocampal neural precursor cells significantly increased,and the apoptotic rates of glial cells reduced,and neuron-like cell differentiation from neural precursor cells significantly increased.Our experimental findings indicate that Jiaweisinisan promotes hippocampal neurogenesis after stress damage.
基金The National Natural Science Foundation of China (grant number 81773891)the National Great New Drugs Development Project of China (grant number 2017ZX09301-040)+1 种基金the Beijing Municipal Science and Technology Commission (grant number XMLX201704, 2018-2-2242, 7194280)the Open Research Fund of the State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicinal Resources.
文摘Quality evaluation is a bottleneck restricting the modernization and internationalization of Chinese materia medica (CMM). Due to characteristics of multi-component, multi-efficacy, multi-target, the existing quality evaluation system still cannot fully meet quality control needs of CMM. Hence, the author put forward “Bio-characteristic profiling related to clinic, BPRC” academic concept, meanwhile, fully take the advantage of analysis method with clinical monitoring superiority or profiling characteristics, build up “BPRC” new technology platform, in order to realize “real-time, dynamic and full-range monitoring” new technologies of CMM quality evaluation system and promote the further development of CMM industry.
基金a Grant from the Ministry of Education of the People’s Republic of China,No.NCET-05-0750a Grant from Guangdong Provincial Natural Science Research Team,No.5200491
文摘in hippocampal neurons is an important contributor to depression. [Ca^2＋]i of hippocampal neurons may raise rapidly with increased corticosterone concentrations, leading to apoptosis. The anti-depressant effects of Xiaoyaosan （Free and Easy Wanderer＇s Powder） may inhibit apoptosis by down regulating the [Ca^2＋]i overload. PC12 cells were containing with corticosterone to simulate neuronal injury, dosed with Xiaoyaosan-containing serum, and the following parameters were measured： apoptosis,[Ca^2＋]i overload, and changes in mitochondrial membrane potential （△ψm） and bioenergetics. High-dose Xiaoyaosan-containing serum （the dose of intragastric administration was 2.633 g herb/mL） not only inhibited morphological injury and cell apoptosis, but also suppressed [Ca^2＋]i overload induced by corticosterone. Xiaoyaosan also blocked the decrease in mitochondrial membrane potential and adenosine triphosphate levels induced by corticosterone. Xiaoyaosan dose-dependently suppresses corticosterone-induced apoptosis, potentially via inhibiting [Ca^2＋]ioverload, and prevents impaired mitochondrial bioenergetics by maintaining mitochondrial membrane potential and adenosine triphosphate production, providing a putative mechanism for its antidepressant effects.
基金supported by the National Natural Science Foundation of China(grant number 81773891)the National Great New Drugs Development Project of China(grant number 2017ZX09301-040)the Beijing Municipal Science and Technology Commission(grant number XMLX201704,2018-2-2242,7194280).
文摘Background:As type 2 diabetes mellitus(T2DM)biomarkers,branched-chain amino acids(BCAAs:valine,leucine and isoleucine)and aromatic amino acids(AAAs:phenylalanine,tryptophan and tyrosine)may be correlated with the occurrence and development of T2DM.However,there is still no consensus on the disperse and isolated biomarkers of T2DM.Purpose:To explore the correlation between amino acids and T2DM based on integrated biomarker approach revealed.Methods:PubMed,Web of Science and CNKI were selected to search the literature published until August 31,2019.The included studies described the association between BCAAs,AAAs and T2DM.Random effect model and fixed effect model were adopted in pooled analysis to determine mean difference and 95 percent confidence interval of metabolites.Integrated biomarker was constructed in form of concentration change ratios or risk ratio(RR),relative risk(HR)and odds ratio(OR)of BCAAs and AAAs to reflect the integrated change information of amino acids.Results:The selected 20 studies contained 14942 healthy individuals and 3615 T2DM patients.The levels of BCAAs,phenylalanine and tyrosine both in plasma and serum samples were increased among all T2DM patients compared with those of the healthy control subjects(P<0.00001).However,the mean difference of tryptophan concentration was not statistically significant(P=0.60).The concentration change ratios or HR/RR/OR of BCAAs and AAAs were connected to form integrated biomarker.Conclusion:The integrated biomarker including BCAAs and AAAs could reflect the basic characteristics of T2DM,which has the potential clinical value on comprehensive diagnosis of T2DM.
