OBJECTIVE Ginsenoside Rb1(Rb1),an important bioactive ingredient of Panax ginseng,has potent neuroprotective effects.The objective of the study is to elucidate the impact of Rb1 treatment on chronic social defeat stre...OBJECTIVE Ginsenoside Rb1(Rb1),an important bioactive ingredient of Panax ginseng,has potent neuroprotective effects.The objective of the study is to elucidate the impact of Rb1 treatment on chronic social defeat stress(CSDS)-induced depressive-like behaviors and its related mechanism.METHODS AND RE⁃SULTS The daily oral administration of Rb1(35 and 70 mg·kg-1)and imipramine(15 mg·kg-1)for 28 d significantly reversed the social avoidance behavior,anhedonia,and behavioral despair via CSDS exposure,as demonstrated by the consid⁃erable elevation in the time in the zone in social interaction test and consumption of sucrose solu⁃tion in sucrose preference test and decrease of immobility time in forced swim test.Moreover,Rb1 obviously restored the CSDS-induced decrease of BDNF-signaling pathway and hippo⁃campal neurogenesis.Rb1 significantly increased the hippocampal levels of ERK,AKT,and CREB phosphorylation and increased the number of DCX+cells in DG.Importantly,the antidepres⁃sant effects of Rb1 were completely blocked in mice by using K252a(the nonselective tyrosine kinase B inhibitor).CONCLUSION Rb1 exerts promising antidepressant-like effects in mice with CSDS-induced depression,and its effects was facilitated by enhancing the BDNF signaling cas⁃cade and up-regulation of hippocampal neuro⁃genesis.展开更多
Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response.Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice ...Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response.Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region–specific,particularly involving the corticolimbic system,including the ventral tegmental area,nucleus accumbens,prefrontal cortex,amygdala,and hippocampus.Determining how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress psychopathology.In this review,we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of depression.We focused on associated molecular pathways and neural circuits,with special attention to the brain-derived neurotrophic factor–tropomyosin receptor kinase B signaling pathway and the ventral tegmental area–nucleus accumbens dopamine circuit.We determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature,severity,and duration of stress,especially in the above-mentioned brain regions of the corticolimbic system.Therefore,BDNF might be a biological indicator regulating stress-related processes in various brain regions.展开更多
OBJECTIVE To explore the pathogenesis of depression according to the LC-MS/MS-based metabolomics in the mouse model which exhibits social avoidance state induced by the chronic social defeat stress model(CSDS).METHODS...OBJECTIVE To explore the pathogenesis of depression according to the LC-MS/MS-based metabolomics in the mouse model which exhibits social avoidance state induced by the chronic social defeat stress model(CSDS).METHODS Twenty male C57BL/6N mice were randomly divided into control group and model group suffering CSDS,and the ICR retired breeder mice were used to attack the model group for 14 d of chronic social defeated stress.The open field test and source preference test were both used to observe depression-like behavior.Besides,the social interaction test is used to observe the social interaction state,especially.After the stress,the serum samples of mice were collected,and the changes of endogenous metabolites were analyzed by LC-MS metabolomics technology,and the pathway analysis of the differential metabolites was performed to explore the pathogenesis of the CSDS induced depressive-like mouse model.RESULTS After the stress of CSDS was completed,the mice in the model group showed a significant slowdown in body weight growth,a reduction in the source preference rate,and a significant reduction in the total distance and the number of rearing in the open field test.Distinctively,the social interaction rate is remarkably decreasing.There are 24 differential metabolites found in the serum of CSDS model mice.CONCLUSION The mouse who suffered CSDS stress would show depressive-like behavior.Based on the LC-MS/MS metabolomics,24 differential metabolites were found in the serum of CSDS model mice.The amino acid metabolism might be significant to the pathogenesis of the CSDS induced depressive-like mouse model.展开更多
Background:Qingyangshen(Cynanchum otophyllum C.K.Schneid)is a folk drug for treating depression and other mental disorders induced by social defeat stress.Neuroplasticity in the hippocampus is essential for the modula...Background:Qingyangshen(Cynanchum otophyllum C.K.Schneid)is a folk drug for treating depression and other mental disorders induced by social defeat stress.Neuroplasticity in the hippocampus is essential for the modulation of cognition and emotion,and its impairment may contribute to the development and progression of depression.Our previous studies have found that Qingyangshen glycosides(QYS)can improve depression-like behavior in social failure mouse models,mainly through PGC-1α/FNDC5/BDNF signaling pathways activation,but its effects and mechanisms on hippocampal neuroplasticity remain unknown.Methods:Chronic social defeat stress(CSDS)was used to induce social defeat in mice.Morphological changes in the hippocampus were observed by H&E staining and Golgi staining.Immunofluorescence double staining was used to detect the expression of synaptophysin(SYN)and postsynaptic density protein-95(PSD-95),while western blot was employed to evaluate PSD-95,SYN,and doublecortin(DCX)proteins.The pathological processing of social defeat and the therapeutic effects of QYS on it was confirmed through behavioral assessment associated with morpho-logic observation.Results:During the whole study,the sucrose preference indices and OFT activity time of CSDS mice were significantly decreased(p≤0.05),and the tail suspension immobil-ity time was significantly increased(p≤0.05),suggesting that the mice had significant depressive symptoms.Treatment with QYS(25,50,and 100 mg/kg)significantly al-leviated depressive symptoms in CSDS mice,which was demonstrated by significantly(p≤0.05 or p≤0.01)reducing the duration of tail-hanging immobility and increasing the tendency of sucrose preference indices and OFT activity time.QYS treatment also significantly increased the expression of DCX,PSD-95,and SYN proteins,which play a crucial role in depression.Conclusions:QYS alleviated these symptoms by enhancing hippocampal neuroplasti-city through upregulating the expression of synapse-associated proteins(SAPs).The therapeutic mechanism of QYS may involve modulating the neuroplasticity of hip-pocampus neurons by altering the expression of SAPs.展开更多
Objective Depression and metabolic disorders have overlapping psychosocial and pathophysiological causes.Current research is focused on the possible role of adiponectin in regulating common biological mechanisms.Xiaoy...Objective Depression and metabolic disorders have overlapping psychosocial and pathophysiological causes.Current research is focused on the possible role of adiponectin in regulating common biological mechanisms.Xiaoyao San(XYS),a classic Chinese medicine compound,has been widely used in the treatment of depression and can alleviate metabolic disorders such as lipid or glucose metabolism disorders.However,the ability of XYS to ameliorate depression-like behavior as well as metabolic dysfunction in mice and the underlying mechanisms are unclear.Methods An in vivo animal model of depression was established by chronic social defeat stress(CSDS).XYS and fluoxetine were administered by gavage to the drug intervention group.Depression-like behaviors were analyzed by the social interaction test,open field test,forced swim test,and elevated plus maze test.Glucose levels were measured using the oral glucose tolerance test.The involvement of certain molecules was validated by immunofluorescence,histopathology,and Western blotting.In vitro,hypothalamic primary neurons were exposed to high glucose to induce neuronal damage,and the neuroprotective effect of XYS was evaluated by cell counting kit-8 assay.Immunofluorescence and Western blotting were used to evaluate the influences of XYS on adiponectin receptor 1(AdipoR1),adenosine 5’-monophosphate-activated protein kinase(AMPK),acetyl-coenzyme A carboxylase(ACC)and other related proteins.Results XYS ameliorated CSDS-induced depression-like behaviors and glucose tolerance impairment in mice and increased the level of serum adiponectin.XYS also restored Nissl bodies in hypothalamic neurons in mice that exhibited depression-like behaviors and decreased the degree of neuronal morphological damage.In vivo and in vitro studies indicated that XYS increased the expression of AdipoR1 in hypothalamic neurons.Conclusion Adiponectin may be a key regulator linking depression and metabolic disorders;regulation of the hypothalamic AdipoR1/AMPK/ACC pathway plays an important role in treatment of depression by XYS.展开更多
基金Ministry of Science and Tech⁃nology of China(2017ZX09301029)and Space Medical Experiment Project of China Manned Space Program(HYZHXM05003)。
文摘OBJECTIVE Ginsenoside Rb1(Rb1),an important bioactive ingredient of Panax ginseng,has potent neuroprotective effects.The objective of the study is to elucidate the impact of Rb1 treatment on chronic social defeat stress(CSDS)-induced depressive-like behaviors and its related mechanism.METHODS AND RE⁃SULTS The daily oral administration of Rb1(35 and 70 mg·kg-1)and imipramine(15 mg·kg-1)for 28 d significantly reversed the social avoidance behavior,anhedonia,and behavioral despair via CSDS exposure,as demonstrated by the consid⁃erable elevation in the time in the zone in social interaction test and consumption of sucrose solu⁃tion in sucrose preference test and decrease of immobility time in forced swim test.Moreover,Rb1 obviously restored the CSDS-induced decrease of BDNF-signaling pathway and hippo⁃campal neurogenesis.Rb1 significantly increased the hippocampal levels of ERK,AKT,and CREB phosphorylation and increased the number of DCX+cells in DG.Importantly,the antidepres⁃sant effects of Rb1 were completely blocked in mice by using K252a(the nonselective tyrosine kinase B inhibitor).CONCLUSION Rb1 exerts promising antidepressant-like effects in mice with CSDS-induced depression,and its effects was facilitated by enhancing the BDNF signaling cas⁃cade and up-regulation of hippocampal neuro⁃genesis.
基金supported financially by the National Natural Science Foundation of China,No.82071272(to YZ).
文摘Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response.Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region–specific,particularly involving the corticolimbic system,including the ventral tegmental area,nucleus accumbens,prefrontal cortex,amygdala,and hippocampus.Determining how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress psychopathology.In this review,we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of depression.We focused on associated molecular pathways and neural circuits,with special attention to the brain-derived neurotrophic factor–tropomyosin receptor kinase B signaling pathway and the ventral tegmental area–nucleus accumbens dopamine circuit.We determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature,severity,and duration of stress,especially in the above-mentioned brain regions of the corticolimbic system.Therefore,BDNF might be a biological indicator regulating stress-related processes in various brain regions.
文摘OBJECTIVE To explore the pathogenesis of depression according to the LC-MS/MS-based metabolomics in the mouse model which exhibits social avoidance state induced by the chronic social defeat stress model(CSDS).METHODS Twenty male C57BL/6N mice were randomly divided into control group and model group suffering CSDS,and the ICR retired breeder mice were used to attack the model group for 14 d of chronic social defeated stress.The open field test and source preference test were both used to observe depression-like behavior.Besides,the social interaction test is used to observe the social interaction state,especially.After the stress,the serum samples of mice were collected,and the changes of endogenous metabolites were analyzed by LC-MS metabolomics technology,and the pathway analysis of the differential metabolites was performed to explore the pathogenesis of the CSDS induced depressive-like mouse model.RESULTS After the stress of CSDS was completed,the mice in the model group showed a significant slowdown in body weight growth,a reduction in the source preference rate,and a significant reduction in the total distance and the number of rearing in the open field test.Distinctively,the social interaction rate is remarkably decreasing.There are 24 differential metabolites found in the serum of CSDS model mice.CONCLUSION The mouse who suffered CSDS stress would show depressive-like behavior.Based on the LC-MS/MS metabolomics,24 differential metabolites were found in the serum of CSDS model mice.The amino acid metabolism might be significant to the pathogenesis of the CSDS induced depressive-like mouse model.
基金Guizhou Administration of TCM,Traditional Chinese medicine,Ethnic Medicine Science and Technology Research Special Project,Grant/Award Number:QZYY-2022-008Subsidy Fund for Scientific Research and Innovation Exploration Project,National Natural Science Foundation of China of Guizhou University of Traditional Chinese Medicine,Grant/Award Number:2018YFC170810502+1 种基金Science and Technology Fund Project of Guizhou Provincial Health Commission,Grant/Award Number:gzwkj2023-147Development of animal models for drug discovery-brain diseases.National Research and Development Project of China,MOST,Grant/Award Number:2023YFF0724802.
文摘Background:Qingyangshen(Cynanchum otophyllum C.K.Schneid)is a folk drug for treating depression and other mental disorders induced by social defeat stress.Neuroplasticity in the hippocampus is essential for the modulation of cognition and emotion,and its impairment may contribute to the development and progression of depression.Our previous studies have found that Qingyangshen glycosides(QYS)can improve depression-like behavior in social failure mouse models,mainly through PGC-1α/FNDC5/BDNF signaling pathways activation,but its effects and mechanisms on hippocampal neuroplasticity remain unknown.Methods:Chronic social defeat stress(CSDS)was used to induce social defeat in mice.Morphological changes in the hippocampus were observed by H&E staining and Golgi staining.Immunofluorescence double staining was used to detect the expression of synaptophysin(SYN)and postsynaptic density protein-95(PSD-95),while western blot was employed to evaluate PSD-95,SYN,and doublecortin(DCX)proteins.The pathological processing of social defeat and the therapeutic effects of QYS on it was confirmed through behavioral assessment associated with morpho-logic observation.Results:During the whole study,the sucrose preference indices and OFT activity time of CSDS mice were significantly decreased(p≤0.05),and the tail suspension immobil-ity time was significantly increased(p≤0.05),suggesting that the mice had significant depressive symptoms.Treatment with QYS(25,50,and 100 mg/kg)significantly al-leviated depressive symptoms in CSDS mice,which was demonstrated by significantly(p≤0.05 or p≤0.01)reducing the duration of tail-hanging immobility and increasing the tendency of sucrose preference indices and OFT activity time.QYS treatment also significantly increased the expression of DCX,PSD-95,and SYN proteins,which play a crucial role in depression.Conclusions:QYS alleviated these symptoms by enhancing hippocampal neuroplasti-city through upregulating the expression of synapse-associated proteins(SAPs).The therapeutic mechanism of QYS may involve modulating the neuroplasticity of hip-pocampus neurons by altering the expression of SAPs.
基金This work was financially supported by the National Natural Science Foundation of China(No.81904091,No.81973748 and No,82174278)the National Natural Science Foundation of Guang-dong,China(No.2021A1515011212)+2 种基金Province Scientific Research Project of Traditional Chinese Medicine Bureau of Guangdong(No.20202039)Huang Zhendong Research Fund for Traditional Chinese Medicine of Jinan University.Key.Area Research and Development Program of Guangdong Province(No.20208111100001)Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine.China.
文摘Objective Depression and metabolic disorders have overlapping psychosocial and pathophysiological causes.Current research is focused on the possible role of adiponectin in regulating common biological mechanisms.Xiaoyao San(XYS),a classic Chinese medicine compound,has been widely used in the treatment of depression and can alleviate metabolic disorders such as lipid or glucose metabolism disorders.However,the ability of XYS to ameliorate depression-like behavior as well as metabolic dysfunction in mice and the underlying mechanisms are unclear.Methods An in vivo animal model of depression was established by chronic social defeat stress(CSDS).XYS and fluoxetine were administered by gavage to the drug intervention group.Depression-like behaviors were analyzed by the social interaction test,open field test,forced swim test,and elevated plus maze test.Glucose levels were measured using the oral glucose tolerance test.The involvement of certain molecules was validated by immunofluorescence,histopathology,and Western blotting.In vitro,hypothalamic primary neurons were exposed to high glucose to induce neuronal damage,and the neuroprotective effect of XYS was evaluated by cell counting kit-8 assay.Immunofluorescence and Western blotting were used to evaluate the influences of XYS on adiponectin receptor 1(AdipoR1),adenosine 5’-monophosphate-activated protein kinase(AMPK),acetyl-coenzyme A carboxylase(ACC)and other related proteins.Results XYS ameliorated CSDS-induced depression-like behaviors and glucose tolerance impairment in mice and increased the level of serum adiponectin.XYS also restored Nissl bodies in hypothalamic neurons in mice that exhibited depression-like behaviors and decreased the degree of neuronal morphological damage.In vivo and in vitro studies indicated that XYS increased the expression of AdipoR1 in hypothalamic neurons.Conclusion Adiponectin may be a key regulator linking depression and metabolic disorders;regulation of the hypothalamic AdipoR1/AMPK/ACC pathway plays an important role in treatment of depression by XYS.
