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
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
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
Social defeat stress(SDS)plays a major role in the pathogenesis of psychiatric disorders like anxiety and depression.Sleep is generally considered to involve recovery of the brain from prior experience during wakefuln...Social defeat stress(SDS)plays a major role in the pathogenesis of psychiatric disorders like anxiety and depression.Sleep is generally considered to involve recovery of the brain from prior experience during wakefulness and is altered after acute SDS.However,the effect of acute SDS on sleep/wake behavior in mice varies between studies.In addition,whether sleep changes in response to stress contribute to anxiety is not well established.Here,we first investigated the effects of acute SDS on sleep/wake states in the active period in mice.Our results showed that total sleep time(time in rapid eyemovement[REM]and non-REM[NREM]sleep)increased in the active period after acute SDS.NREM sleep increased mainly during the first 3 h after SDS,while REM sleep increased at a later time.Then,we demonstrated that the increased NREM sleep had an anxiolytic benefit in acute SDS.Mice deprived of sleep for 1 h or 3 h after acute SDS remained in a highly anxious state,while in mice with ad libitum sleep the anxiety rapidly faded away.Altogether,our findings suggest an anxiolytic effect of NREM sleep,and indicate a potential therapeutic strategy for anxiety.展开更多
Objective:Psychosocial stress has been implicated in the genesis of psychiatric disorders such as memory deficits,depression,anxiety and addiction.Aqueous leaf extract of Cymbopogon citratus(CYC)otherwise known as lem...Objective:Psychosocial stress has been implicated in the genesis of psychiatric disorders such as memory deficits,depression,anxiety and addiction.Aqueous leaf extract of Cymbopogon citratus(CYC)otherwise known as lemongrass tea has antidepressant,anxiolytic and anti-amnesic effects in rodents.This study was designed to evaluate if C citratus could reverse the neurobehavioral and biochemical derangements induced by social defeat stress(SDS)in the resident/intruder paradigm.Methods:Intruder male mice were divided into five groups(n=7):group 1 received saline(10 mL/kg,p.o.;non-stress control),group 2 also received saline(10 mL/kg,p.o.;SDS control)while groups 3-5 had C.citratus(50,100 and 200 mg/kg,p.o.)daily for 14 d.The SDS was carried out 30 min after each treatment from day 7 to day 14 by exposing each intruder mouse in groups 2-5 to a 10 min confrontation in the home cage of an aggressive resident counterpart.The neurobehavioral features(spontaneous motor activity-SMA,anxiety,memory,social avoidance and depression were then evaluated.The concentrations of nitrite,malondialdehyde and glutathione as well as acetylcholinesterase activity in the brain tissues were also determined.Results:C.citratus(50,100 and 200 mg/kg)attenuated hypolocomotion,heightened anxiety,depressive-like symptom,memory deficit and social avoidance induced by SDS.The altered levels of oxidative stress and acetyl-cholinesterase in SDS-mice were positively modulated by C.citratus.Conclusion:The results of this study suggest that C.citratus might mitigate psychosocial stress-induced neurologic diseases in susceptible individuals.展开更多
The aim of the present study was to investigate the effects of the anti-asthenic drug ladasten on behavioral patterns and T-cell subsets in blood, spleen, and thymus in socially stressed male C57Bl/6 mice. Mice subjec...The aim of the present study was to investigate the effects of the anti-asthenic drug ladasten on behavioral patterns and T-cell subsets in blood, spleen, and thymus in socially stressed male C57Bl/6 mice. Mice subjected to social defeat stress (SDS) for 25 days developed a depressive-like phenotype. The submissive SDS animals were assigned to one of two treatment groups: one group was treated with ladasten (30 mg/kg, i.p.) for up to 5 days, and the other one was administered vehicle as a control. Twenty four hours after the last injection, behavioral parameters were tested, and trunk blood and tissue samples were collected. SDS mice from the vehicle-treated group showed a subordinate and passive avoidance behavior with significantly decreased spontaneous locomotor activity (SLA) and exhibited impaired parameters in the forced swimming test (FST). Changes in behavioral status were correlated with an increase spleen weight, a decrease in thymic index and a shift in the CD4/CD8 balance toward T-cytotoxic cells. The behavior parameters were reversed in the group treated with ladasten compared to the untreated SDS group and were similar to those of unstressed mice. Treatment of socially stressed mice with ladasten normalized the amount of T-lymphocyte cells in the blood, spleen, and thymus. These findings support the notion that depression is accompanied by cell-mediated immune activation and that targeting this pathway may be a new therapeutic approach for treatment. Furthermore, our data support further investigations of ladasten as a potent anti-depressive drug which can be used alone as well as in combination with other anti-depressants.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.
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.
基金This work was supported by the National Key Research and Development Program of China(2016YFA0501000 and 2016YFC1306700)the National Natural Science Foundation of China(31970939,81527901,81821091,31771167,31571090,and 31490592)+2 种基金the Science and Technology Planning Project of Guangdong Province of China(2018B030331001)the Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences(2018PT31041)and Fundamental Research Funds for the Central Universities,China(2017FZA7003).
文摘Social defeat stress(SDS)plays a major role in the pathogenesis of psychiatric disorders like anxiety and depression.Sleep is generally considered to involve recovery of the brain from prior experience during wakefulness and is altered after acute SDS.However,the effect of acute SDS on sleep/wake behavior in mice varies between studies.In addition,whether sleep changes in response to stress contribute to anxiety is not well established.Here,we first investigated the effects of acute SDS on sleep/wake states in the active period in mice.Our results showed that total sleep time(time in rapid eyemovement[REM]and non-REM[NREM]sleep)increased in the active period after acute SDS.NREM sleep increased mainly during the first 3 h after SDS,while REM sleep increased at a later time.Then,we demonstrated that the increased NREM sleep had an anxiolytic benefit in acute SDS.Mice deprived of sleep for 1 h or 3 h after acute SDS remained in a highly anxious state,while in mice with ad libitum sleep the anxiety rapidly faded away.Altogether,our findings suggest an anxiolytic effect of NREM sleep,and indicate a potential therapeutic strategy for anxiety.
文摘Objective:Psychosocial stress has been implicated in the genesis of psychiatric disorders such as memory deficits,depression,anxiety and addiction.Aqueous leaf extract of Cymbopogon citratus(CYC)otherwise known as lemongrass tea has antidepressant,anxiolytic and anti-amnesic effects in rodents.This study was designed to evaluate if C citratus could reverse the neurobehavioral and biochemical derangements induced by social defeat stress(SDS)in the resident/intruder paradigm.Methods:Intruder male mice were divided into five groups(n=7):group 1 received saline(10 mL/kg,p.o.;non-stress control),group 2 also received saline(10 mL/kg,p.o.;SDS control)while groups 3-5 had C.citratus(50,100 and 200 mg/kg,p.o.)daily for 14 d.The SDS was carried out 30 min after each treatment from day 7 to day 14 by exposing each intruder mouse in groups 2-5 to a 10 min confrontation in the home cage of an aggressive resident counterpart.The neurobehavioral features(spontaneous motor activity-SMA,anxiety,memory,social avoidance and depression were then evaluated.The concentrations of nitrite,malondialdehyde and glutathione as well as acetylcholinesterase activity in the brain tissues were also determined.Results:C.citratus(50,100 and 200 mg/kg)attenuated hypolocomotion,heightened anxiety,depressive-like symptom,memory deficit and social avoidance induced by SDS.The altered levels of oxidative stress and acetyl-cholinesterase in SDS-mice were positively modulated by C.citratus.Conclusion:The results of this study suggest that C.citratus might mitigate psychosocial stress-induced neurologic diseases in susceptible individuals.
文摘The aim of the present study was to investigate the effects of the anti-asthenic drug ladasten on behavioral patterns and T-cell subsets in blood, spleen, and thymus in socially stressed male C57Bl/6 mice. Mice subjected to social defeat stress (SDS) for 25 days developed a depressive-like phenotype. The submissive SDS animals were assigned to one of two treatment groups: one group was treated with ladasten (30 mg/kg, i.p.) for up to 5 days, and the other one was administered vehicle as a control. Twenty four hours after the last injection, behavioral parameters were tested, and trunk blood and tissue samples were collected. SDS mice from the vehicle-treated group showed a subordinate and passive avoidance behavior with significantly decreased spontaneous locomotor activity (SLA) and exhibited impaired parameters in the forced swimming test (FST). Changes in behavioral status were correlated with an increase spleen weight, a decrease in thymic index and a shift in the CD4/CD8 balance toward T-cytotoxic cells. The behavior parameters were reversed in the group treated with ladasten compared to the untreated SDS group and were similar to those of unstressed mice. Treatment of socially stressed mice with ladasten normalized the amount of T-lymphocyte cells in the blood, spleen, and thymus. These findings support the notion that depression is accompanied by cell-mediated immune activation and that targeting this pathway may be a new therapeutic approach for treatment. Furthermore, our data support further investigations of ladasten as a potent anti-depressive drug which can be used alone as well as in combination with other anti-depressants.
