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
[Objectives]To explore the antidepressant effect of Shenwei Ningyu Tablet,a new antidepressant traditional Chinese medicine,on rat chronic stress depression model and mouse tail suspension models.[Methods]Rat chronic ...[Objectives]To explore the antidepressant effect of Shenwei Ningyu Tablet,a new antidepressant traditional Chinese medicine,on rat chronic stress depression model and mouse tail suspension models.[Methods]Rat chronic stress model:except for the normal group,the rats in other groups were given corresponding chronic stress,and administered by gavage 1 h before modeling,for a total of 21 d.The changes of each indicator before and after the experiment were observed through the body weight change,the sugar water test,and open field test.The relevant hormone levels were detected by radioimmunoassay.Mouse tail suspension depression model:after continuous administration for 7 d,the activity times was recorded with the mouse automatic recorder,and the mouse immobility time was recorded after tail suspension,to explore the effects of each administration group on the tail suspension immobility time of mice.[Results]Chronic stress depression model:21 d after modeling,compared with the normal group,rats in the model group exhibited significantly reduced body weight,sucrose preference index,and horizontal and vertical movement scores(P<0.05).Compared with the model group,the low-dose Shenwei Ningyu Tablets group had significant differences in the sugar water test,horizontal and vertical movement scores(P<0.05).In addition,all three dose groups of Shenwei Ningyu Tablets could effectively reduce the content of CRF in chronic stress model rats,and the low dose group could significantly reduce the ACTH level in model rats(P<0.05).Mouse tail suspension depression model:the immobility time after tail suspension in each administration group was significantly different from that in the model group(P<0.05).[Conclusions]Shenwei Ningyu Tablets has a certain anti-depression effect on both the rat chronic stress depression model and the mouse tail suspension depression model.展开更多
The postpartum period is when a host of changes occur at molecular, cellular, physiological and behavioral levels to prepare female humans for the challenge of maternity. Alteration or prevention of these normal adapt...The postpartum period is when a host of changes occur at molecular, cellular, physiological and behavioral levels to prepare female humans for the challenge of maternity. Alteration or prevention of these normal adaptions is thought to contribute to disruptions of emotion regulation, motivation and cognitive abilities that underlie postpartum mental disorders, such as postpartum depression. Despite the high incidence of this disorder, and the detrimental consequences for both mother and child, its etiology and related neurobiological mechanisms remain poorly understood, partially due to the lack of appropriate animal models. In recent decades, there have been a number of attempts to model postpartum depression disorder in rats. In the present review, we first describe clinical symptoms of postpartum depression and discuss known risk factors, including both genetic and environmental factors. Thereafter, we discuss various rat models that have been developed to capture various aspects of this disorder and knowledge gained from such attempts. In doing so, we focus on the theories behind each attempt and the methods used to achieve their goals. Finally, we point out several understudied areas in this field and make suggestions for future directions.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
目的:抑郁症是全球疾病负担的五大主要原因之一,目前可用的抗抑郁药物疗效低、起效慢、不良反应严重,而运动是治疗抑郁症的一种较好的方式。文章系统评价了运动对慢性不可预知轻度应激(CUMS)模型鼠抑郁相关行为的干预效果。方法:检索万...目的:抑郁症是全球疾病负担的五大主要原因之一,目前可用的抗抑郁药物疗效低、起效慢、不良反应严重,而运动是治疗抑郁症的一种较好的方式。文章系统评价了运动对慢性不可预知轻度应激(CUMS)模型鼠抑郁相关行为的干预效果。方法:检索万方、中国知网、PubMed、Embase和Web of Science数据库,检索文献时限为2000-01-01/2022-02-28,收集跑台、游泳、转轮等运动对慢性不可预知轻度应激(CUMS)抑郁动物模型强迫游泳、悬尾、糖水偏好行为学影响的研究。由2位研究者按照纳入标准独立完成文献筛选、资料提取及SYRCLE动物实验偏倚风险评估工具进行方法学质量评价,运用RevMan 5.3和Stata 13.0分析软件进行统计分析。结果:共纳入23篇对照动物实验文献,运动组实验动物301只,对照组302只。Meta分析结果显示:①运动能够显著降低抑郁模型鼠强迫游泳测试潜伏期[SMD=-3.93,95%CI:(-4.88,-2.98),P<0.00001]及悬尾测试潜伏期[SMD=-4.42,95%CI:(-5.62,-3.23),P<0.00001];②运动同样可以提高糖水偏好指数[SMD=2.37,95%CI:(1.62,3.11),P<0.00001];③悬尾测试中对运动方式进行亚组分析可以降低异质性[SMD=-3.68,95%CI:(-4.16,-3.21),P<0.00001],但并不影响运动效果。结论:运动能有效改善慢性不可预知轻度应激(CUMS)模型鼠强迫游泳、悬尾、糖水偏好的抑郁样行为。运动方式可能是影响悬尾测试行为的异质性来源;造模时间、干预阶段、运动方式及运动时间不是影响运动改善抑郁效果的主要因素。展开更多
Depression is a chronic,recurring and potentially life-threatening illness that affects up to 20%of the population across the world.Despite its prevalence and considerable impact on human,little is known about its pat...Depression is a chronic,recurring and potentially life-threatening illness that affects up to 20%of the population across the world.Despite its prevalence and considerable impact on human,little is known about its pathogenesis.One of the major reasons is the restricted availability of validated animal models due to the absence of consensus on the pathology and etiology of depression.Besides,some core symptoms such as depressed mood,feeling of worthlessness,and recurring thoughts of death or suicide,are impossible to be modeled on laboratory animals.Currently,the criteria for identifying animal models of depression rely on either of the 2 principles：actions of known antidepressants and responses to stress.This review mainly focuses on the most widely used animal models of depression,including learned helplessness,chronic mild stress,and social defeat paradigms.Also,the behavioral tests for screening antidepressants,such as forced swimming test and tail suspension test,are also discussed.The advantages and major drawbacks of each model are evaluated.In prospective,new techniques that will be beneficial for developing novel animal models or detecting depression are discussed.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National Major Scientific and Technological Special Project for"Significant New Drugs Development"(2019ZX09301-005).
文摘[Objectives]To explore the antidepressant effect of Shenwei Ningyu Tablet,a new antidepressant traditional Chinese medicine,on rat chronic stress depression model and mouse tail suspension models.[Methods]Rat chronic stress model:except for the normal group,the rats in other groups were given corresponding chronic stress,and administered by gavage 1 h before modeling,for a total of 21 d.The changes of each indicator before and after the experiment were observed through the body weight change,the sugar water test,and open field test.The relevant hormone levels were detected by radioimmunoassay.Mouse tail suspension depression model:after continuous administration for 7 d,the activity times was recorded with the mouse automatic recorder,and the mouse immobility time was recorded after tail suspension,to explore the effects of each administration group on the tail suspension immobility time of mice.[Results]Chronic stress depression model:21 d after modeling,compared with the normal group,rats in the model group exhibited significantly reduced body weight,sucrose preference index,and horizontal and vertical movement scores(P<0.05).Compared with the model group,the low-dose Shenwei Ningyu Tablets group had significant differences in the sugar water test,horizontal and vertical movement scores(P<0.05).In addition,all three dose groups of Shenwei Ningyu Tablets could effectively reduce the content of CRF in chronic stress model rats,and the low dose group could significantly reduce the ACTH level in model rats(P<0.05).Mouse tail suspension depression model:the immobility time after tail suspension in each administration group was significantly different from that in the model group(P<0.05).[Conclusions]Shenwei Ningyu Tablets has a certain anti-depression effect on both the rat chronic stress depression model and the mouse tail suspension depression model.
基金Foundation items： The preparation of this review was partially supported by a grant from the National Institute of Mental Health （5R01 MH097718-02）, U.S.A.
文摘The postpartum period is when a host of changes occur at molecular, cellular, physiological and behavioral levels to prepare female humans for the challenge of maternity. Alteration or prevention of these normal adaptions is thought to contribute to disruptions of emotion regulation, motivation and cognitive abilities that underlie postpartum mental disorders, such as postpartum depression. Despite the high incidence of this disorder, and the detrimental consequences for both mother and child, its etiology and related neurobiological mechanisms remain poorly understood, partially due to the lack of appropriate animal models. In recent decades, there have been a number of attempts to model postpartum depression disorder in rats. In the present review, we first describe clinical symptoms of postpartum depression and discuss known risk factors, including both genetic and environmental factors. Thereafter, we discuss various rat models that have been developed to capture various aspects of this disorder and knowledge gained from such attempts. In doing so, we focus on the theories behind each attempt and the methods used to achieve their goals. Finally, we point out several understudied areas in this field and make suggestions for future directions.
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.
文摘目的:抑郁症是全球疾病负担的五大主要原因之一,目前可用的抗抑郁药物疗效低、起效慢、不良反应严重,而运动是治疗抑郁症的一种较好的方式。文章系统评价了运动对慢性不可预知轻度应激(CUMS)模型鼠抑郁相关行为的干预效果。方法:检索万方、中国知网、PubMed、Embase和Web of Science数据库,检索文献时限为2000-01-01/2022-02-28,收集跑台、游泳、转轮等运动对慢性不可预知轻度应激(CUMS)抑郁动物模型强迫游泳、悬尾、糖水偏好行为学影响的研究。由2位研究者按照纳入标准独立完成文献筛选、资料提取及SYRCLE动物实验偏倚风险评估工具进行方法学质量评价,运用RevMan 5.3和Stata 13.0分析软件进行统计分析。结果:共纳入23篇对照动物实验文献,运动组实验动物301只,对照组302只。Meta分析结果显示:①运动能够显著降低抑郁模型鼠强迫游泳测试潜伏期[SMD=-3.93,95%CI:(-4.88,-2.98),P<0.00001]及悬尾测试潜伏期[SMD=-4.42,95%CI:(-5.62,-3.23),P<0.00001];②运动同样可以提高糖水偏好指数[SMD=2.37,95%CI:(1.62,3.11),P<0.00001];③悬尾测试中对运动方式进行亚组分析可以降低异质性[SMD=-3.68,95%CI:(-4.16,-3.21),P<0.00001],但并不影响运动效果。结论:运动能有效改善慢性不可预知轻度应激(CUMS)模型鼠强迫游泳、悬尾、糖水偏好的抑郁样行为。运动方式可能是影响悬尾测试行为的异质性来源;造模时间、干预阶段、运动方式及运动时间不是影响运动改善抑郁效果的主要因素。
文摘Depression is a chronic,recurring and potentially life-threatening illness that affects up to 20%of the population across the world.Despite its prevalence and considerable impact on human,little is known about its pathogenesis.One of the major reasons is the restricted availability of validated animal models due to the absence of consensus on the pathology and etiology of depression.Besides,some core symptoms such as depressed mood,feeling of worthlessness,and recurring thoughts of death or suicide,are impossible to be modeled on laboratory animals.Currently,the criteria for identifying animal models of depression rely on either of the 2 principles：actions of known antidepressants and responses to stress.This review mainly focuses on the most widely used animal models of depression,including learned helplessness,chronic mild stress,and social defeat paradigms.Also,the behavioral tests for screening antidepressants,such as forced swimming test and tail suspension test,are also discussed.The advantages and major drawbacks of each model are evaluated.In prospective,new techniques that will be beneficial for developing novel animal models or detecting depression are discussed.
