Replica scaled impact experiments with unconfined ceramic targets have shown that the transition velocity,i.e.,the impact velocity at which interface defeat ceases and ceramic penetration occurs,decreased as the lengt...Replica scaled impact experiments with unconfined ceramic targets have shown that the transition velocity,i.e.,the impact velocity at which interface defeat ceases and ceramic penetration occurs,decreased as the length scale increased.A possible explanation of how this scale effect is related to the formation of a cone crack in the ceramic has been presented by the authors in an earlier paper.Here,the influence of confinement and prestress on cone cracking and transition velocity is investigated.The hypothesis is that prestress will suppress the formation and growth of the cone crack by lowering the driving stress.A set of impact experiments has been performed in which the transition velocity for four different levels of prestress has been determined.The transition velocities as a function of the level of confining prestress is compared to an analytical model for the influence of prestress on the formation and extension of the cone crack in the ceramic material.Both experiments and model indicate that prestress has a strong influence on the transition from interface defeat to penetration,although the model underestimates the influence of prestress.展开更多
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
The interface defeat phenomenon always occurs when a long-rod projectile impacting on the ceramic target with certain velocity,i.e.,the projectile is forced to flow radially on the surface of ceramic plates for a peri...The interface defeat phenomenon always occurs when a long-rod projectile impacting on the ceramic target with certain velocity,i.e.,the projectile is forced to flow radially on the surface of ceramic plates for a period of time without significant penetration.Interface defeat has a direct effect upon the ballistic performance of the armor piercing projectile,which is studied numerically and theoretically at present.Firstly,by modeling the projectiles and ceramic targets with the SPH(Smoothed Particle Hydrodynamics)particles and Lagrange finite elements,the systematic numerical simulations on interface defeat are performed with the commercial finite element program AUTODYN.Three different responses,i.e.,complete interface defeat,dwell and direct penetration,are reproduced in different types of ceramic targets(bare,buffered,radially confined and oblique).Furthermore,by adopting the validated numerical algorithms,constitutive models and the corresponding material parameters,the influences of projectile(material,diameter,nose shape),constitutive models of ceramic(JH-1 and JH-2 models),buffer and cover plate(thickness,constraints,material),as well as the prestress acted on the target(radial and hydrostatic) on the interface defeat(transition velocity and dwell time) are syste matically investigated.Finally,based on the energy conservation approach and taking the strain rate effect of ceramic material into account,a modified model for predicting the upper limit of transition velocity is proposed and validated.The present work and derived conclusions can provide helpful reference for the design and optimization of both the long-rod projectile and ceramic armor.展开更多
Despite all the human efforts and monetary investment over the last few decades,cancer is still a devastating threat to our life expectancy and quality of life in many parts of the world.The etiology of cancer varies....Despite all the human efforts and monetary investment over the last few decades,cancer is still a devastating threat to our life expectancy and quality of life in many parts of the world.The etiology of cancer varies.The genetic and epigenetic causes of cancer are heterogeneous and multifaceted.Early detection is still a展开更多
Chronic social defeat stress induces diverse effects in mice of different strains and even in animals of the same strain. This paper aims to study the effect of repeated social defeats and, for contrast, repeated aggr...Chronic social defeat stress induces diverse effects in mice of different strains and even in animals of the same strain. This paper aims to study the effect of repeated social defeats and, for contrast, repeated aggression in daily agonistic interactions on the behaviors of CD-1 male mice. The behavior of animals that have the same winning and losing track record during 3, 10, 21 days is studied in different tests. The level of aggressiveness, as estimated by the number and total time of attacks, decreases;nevertheless, direct and indirect forms of aggression demonstrated by the aggressive mice (winners) remain significantly high. The number of stereotypic behaviors (rotations and jumps) and total time of digging behaviors are significantly increased in the winners after 21 days compared to 3 and 10 days of intermale confrontations. Among the losers, chronic experience of social defeats is accompanied by the development of pronounced anxiety and a depression-like state estimated by the elevated plus-maze and the Porsolt test scores, respectively. Both groups of male mice with alternative social behaviors demonstrate abnormal locomotor and exploratory behaviors in the open-field test. This phenomenon may be viewed as hyperactivity developed under chronic agonistic interactions and specific for the outbred CD-1 mice. We believe that these animals may be potentially used for modeling the key symptoms of bipolar disorder.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
OBJECTIVEα-Dstroglycan(α-DG)is a predominant component in the dystrophin-glycoprotein complex(DGC)and a recently char⁃acterized receptor for several extracellular matrix components with high affinity.Recent research...OBJECTIVEα-Dstroglycan(α-DG)is a predominant component in the dystrophin-glycoprotein complex(DGC)and a recently char⁃acterized receptor for several extracellular matrix components with high affinity.Recent research⁃es have reported that hypoglycosylation ofα-DG is associated with the pathophysiology of diseas⁃es,especially muscular dystrophy,but little is known about major depressive disorder(MDD).Like-acetylglucosaminyl transferase(Large)is a key enzyme for glycosylation ofα-DG,which mainly modifies two points in the middle domain ofα-DG:Thr-317 and Thr-319.Glycosylatedα-DG(GLY-α-DG)can bind with high affinity to extracellular matrix(ECM)molecules that con⁃tain laminin globular(LG)domains,including per⁃lecan,agrin and neurexin.Agrin is mainly derived from neurons rather than glial cells.In cultured hippocampal neurons,it was found that agrin could regulate the homeostatic plasticity of inhibi⁃tory neurons by acting on GLY-α-DG.Mdx mice are transgenetic models for the investigation of Duchenne muscular dystrophy.Many studies have shown that the expression of GLY-α-DG in the peripheral and brain tissues of Mdx mice is significantly down-regulated.Mdx mice show cognitive impairment and high levels of anxiety.In this study,we employed chronic social defeat stress(CSDS)to establish an animal model of depression and detected the expression of GLY-α-DG among the brain areas associated with the pathophysiology of depression.METHODS So⁃cial interaction test(SIT)and sucrose preference test(SPT)were used to evaluate depressive-like behavior.Open field(OF)and elevated plus maze(EPM)test were used to determine the anxiety-like behavior of Mdx mice.Novelty-sup⁃pressed feeding test(NSFT)forced swim test(FST)and tail suspension test(TST)were used to detect the depressive-like behavior of Mdx mice.Novel object recognition test(NOR)was applied to evaluate the cognition of Mdx mice.Subthreshold social defeat stress was used to explore the susceptibility to stress in Mdx mice.Stereotactic infusion of agrin into the ventral hippocampus(vHip),FST and TST were used to investigate the antidepressant effects of agrin.Adeno-associated virus(AAV)-mediated overex⁃pression techniques,behavior tests and whole-cell path-clamp technique were conducted to determine the impact of Large overexpression on CSDS susceptible mice.RESULTS The expres⁃sion ofα-DG and GLY-α-DG were significantly decreased in the vHip of CSDS susceptible mice.Mdx mice showed decreased expression of GLY-α-DG and increased anxiety-like behav⁃iors.Mdx mice displayed some depressive-like behaviors,and the susceptibility to stress was significantly increased.Downregulation of the expressionα-DG in the vHip by lentivirus increased the susceptibility to stress.Administra⁃tion of agrin to CSDS susceptible mice exerted antidepressant effects,and this effect could par⁃tially sustain for a week.The expression of Large was decreased in vHip.Overexpression of Large through AAV-Large reversed the depressive-like behaviors and restored the decreased frequency and amplitude of mIPSC.CONCLUSION GLY-α-DG and its glycosylase are significantly decreased in CSDS susceptible mice.Adminis⁃tration of agrin and overexpression of Large displays antidepressant effect,which may be related to its promotion of inhibitory synaptic transmission.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
Old fisherman Santiago fight bravely,the battle he loses in the flesh can be one he wins in the spirit.The old man should be regarded as a noble hero,if tragic,a failure for his physical suffers and loses of the big f...Old fisherman Santiago fight bravely,the battle he loses in the flesh can be one he wins in the spirit.The old man should be regarded as a noble hero,if tragic,a failure for his physical suffers and loses of the big fish,not a failure for his spirit of optimism,confidence,wisdom of spirits,perseverance and bravery.He wins the interior triumph from physical defeat.Whether to be a triumphed hero or a defeated failure is up to a person's efforts.展开更多
AFRICAN women have been making headlines this year, with South Africa＇s Home Affairs Minister Nkosazama Dhlamini-Zuma lobbying for the post of African Union chief, Joyce Banda being sworn in as Malawi president and n...AFRICAN women have been making headlines this year, with South Africa＇s Home Affairs Minister Nkosazama Dhlamini-Zuma lobbying for the post of African Union chief, Joyce Banda being sworn in as Malawi president and now Nigeria＇s Ngozi Okonjo-Iweala nominated for the top job at the World Bank.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
基金funded by the Swedish Armed Forces and by the Army Research Laboratory through US Naval Regional Contracting Centre,Contract No.W911NF0810271
文摘Replica scaled impact experiments with unconfined ceramic targets have shown that the transition velocity,i.e.,the impact velocity at which interface defeat ceases and ceramic penetration occurs,decreased as the length scale increased.A possible explanation of how this scale effect is related to the formation of a cone crack in the ceramic has been presented by the authors in an earlier paper.Here,the influence of confinement and prestress on cone cracking and transition velocity is investigated.The hypothesis is that prestress will suppress the formation and growth of the cone crack by lowering the driving stress.A set of impact experiments has been performed in which the transition velocity for four different levels of prestress has been determined.The transition velocities as a function of the level of confining prestress is compared to an analytical model for the influence of prestress on the formation and extension of the cone crack in the ceramic material.Both experiments and model indicate that prestress has a strong influence on the transition from interface defeat to penetration,although the model underestimates the influence of prestress.
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 by the National Natural Science Foundation of China(51878507)。
文摘The interface defeat phenomenon always occurs when a long-rod projectile impacting on the ceramic target with certain velocity,i.e.,the projectile is forced to flow radially on the surface of ceramic plates for a period of time without significant penetration.Interface defeat has a direct effect upon the ballistic performance of the armor piercing projectile,which is studied numerically and theoretically at present.Firstly,by modeling the projectiles and ceramic targets with the SPH(Smoothed Particle Hydrodynamics)particles and Lagrange finite elements,the systematic numerical simulations on interface defeat are performed with the commercial finite element program AUTODYN.Three different responses,i.e.,complete interface defeat,dwell and direct penetration,are reproduced in different types of ceramic targets(bare,buffered,radially confined and oblique).Furthermore,by adopting the validated numerical algorithms,constitutive models and the corresponding material parameters,the influences of projectile(material,diameter,nose shape),constitutive models of ceramic(JH-1 and JH-2 models),buffer and cover plate(thickness,constraints,material),as well as the prestress acted on the target(radial and hydrostatic) on the interface defeat(transition velocity and dwell time) are syste matically investigated.Finally,based on the energy conservation approach and taking the strain rate effect of ceramic material into account,a modified model for predicting the upper limit of transition velocity is proposed and validated.The present work and derived conclusions can provide helpful reference for the design and optimization of both the long-rod projectile and ceramic armor.
文摘Despite all the human efforts and monetary investment over the last few decades,cancer is still a devastating threat to our life expectancy and quality of life in many parts of the world.The etiology of cancer varies.The genetic and epigenetic causes of cancer are heterogeneous and multifaceted.Early detection is still a
文摘Chronic social defeat stress induces diverse effects in mice of different strains and even in animals of the same strain. This paper aims to study the effect of repeated social defeats and, for contrast, repeated aggression in daily agonistic interactions on the behaviors of CD-1 male mice. The behavior of animals that have the same winning and losing track record during 3, 10, 21 days is studied in different tests. The level of aggressiveness, as estimated by the number and total time of attacks, decreases;nevertheless, direct and indirect forms of aggression demonstrated by the aggressive mice (winners) remain significantly high. The number of stereotypic behaviors (rotations and jumps) and total time of digging behaviors are significantly increased in the winners after 21 days compared to 3 and 10 days of intermale confrontations. Among the losers, chronic experience of social defeats is accompanied by the development of pronounced anxiety and a depression-like state estimated by the elevated plus-maze and the Porsolt test scores, respectively. Both groups of male mice with alternative social behaviors demonstrate abnormal locomotor and exploratory behaviors in the open-field test. This phenomenon may be viewed as hyperactivity developed under chronic agonistic interactions and specific for the outbred CD-1 mice. We believe that these animals may be potentially used for modeling the key symptoms of bipolar disorder.
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.
文摘OBJECTIVEα-Dstroglycan(α-DG)is a predominant component in the dystrophin-glycoprotein complex(DGC)and a recently char⁃acterized receptor for several extracellular matrix components with high affinity.Recent research⁃es have reported that hypoglycosylation ofα-DG is associated with the pathophysiology of diseas⁃es,especially muscular dystrophy,but little is known about major depressive disorder(MDD).Like-acetylglucosaminyl transferase(Large)is a key enzyme for glycosylation ofα-DG,which mainly modifies two points in the middle domain ofα-DG:Thr-317 and Thr-319.Glycosylatedα-DG(GLY-α-DG)can bind with high affinity to extracellular matrix(ECM)molecules that con⁃tain laminin globular(LG)domains,including per⁃lecan,agrin and neurexin.Agrin is mainly derived from neurons rather than glial cells.In cultured hippocampal neurons,it was found that agrin could regulate the homeostatic plasticity of inhibi⁃tory neurons by acting on GLY-α-DG.Mdx mice are transgenetic models for the investigation of Duchenne muscular dystrophy.Many studies have shown that the expression of GLY-α-DG in the peripheral and brain tissues of Mdx mice is significantly down-regulated.Mdx mice show cognitive impairment and high levels of anxiety.In this study,we employed chronic social defeat stress(CSDS)to establish an animal model of depression and detected the expression of GLY-α-DG among the brain areas associated with the pathophysiology of depression.METHODS So⁃cial interaction test(SIT)and sucrose preference test(SPT)were used to evaluate depressive-like behavior.Open field(OF)and elevated plus maze(EPM)test were used to determine the anxiety-like behavior of Mdx mice.Novelty-sup⁃pressed feeding test(NSFT)forced swim test(FST)and tail suspension test(TST)were used to detect the depressive-like behavior of Mdx mice.Novel object recognition test(NOR)was applied to evaluate the cognition of Mdx mice.Subthreshold social defeat stress was used to explore the susceptibility to stress in Mdx mice.Stereotactic infusion of agrin into the ventral hippocampus(vHip),FST and TST were used to investigate the antidepressant effects of agrin.Adeno-associated virus(AAV)-mediated overex⁃pression techniques,behavior tests and whole-cell path-clamp technique were conducted to determine the impact of Large overexpression on CSDS susceptible mice.RESULTS The expres⁃sion ofα-DG and GLY-α-DG were significantly decreased in the vHip of CSDS susceptible mice.Mdx mice showed decreased expression of GLY-α-DG and increased anxiety-like behav⁃iors.Mdx mice displayed some depressive-like behaviors,and the susceptibility to stress was significantly increased.Downregulation of the expressionα-DG in the vHip by lentivirus increased the susceptibility to stress.Administra⁃tion of agrin to CSDS susceptible mice exerted antidepressant effects,and this effect could par⁃tially sustain for a week.The expression of Large was decreased in vHip.Overexpression of Large through AAV-Large reversed the depressive-like behaviors and restored the decreased frequency and amplitude of mIPSC.CONCLUSION GLY-α-DG and its glycosylase are significantly decreased in CSDS susceptible mice.Adminis⁃tration of agrin and overexpression of Large displays antidepressant effect,which may be related to its promotion of inhibitory synaptic transmission.
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.
文摘Old fisherman Santiago fight bravely,the battle he loses in the flesh can be one he wins in the spirit.The old man should be regarded as a noble hero,if tragic,a failure for his physical suffers and loses of the big fish,not a failure for his spirit of optimism,confidence,wisdom of spirits,perseverance and bravery.He wins the interior triumph from physical defeat.Whether to be a triumphed hero or a defeated failure is up to a person's efforts.
文摘AFRICAN women have been making headlines this year, with South Africa＇s Home Affairs Minister Nkosazama Dhlamini-Zuma lobbying for the post of African Union chief, Joyce Banda being sworn in as Malawi president and now Nigeria＇s Ngozi Okonjo-Iweala nominated for the top job at the World Bank.
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.
