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
Objective:To establish a mouse model of affective disorder complicated with atherosclerosis(AS)by high fat feeding and chronic mild unpredictable stimulation(CUMS),and to provide an animal model for the later study of...Objective:To establish a mouse model of affective disorder complicated with atherosclerosis(AS)by high fat feeding and chronic mild unpredictable stimulation(CUMS),and to provide an animal model for the later study of the prevention and treatment of affective disorder complicated with atherosclerosis by traditional Chinese medicine.Methods:10 C57BL/6J mice were used as blank group,and 20 ApoE-/-mice were randomly divided into AS group and AS+CUMS group.After one week of adaptive feeding,except for the blank group,the other two groups were fed with high fat diet.Meanwhile,the AS+CUMS group was given chronic unpredictable mild stress.The model was evaluated after 16 weeks of modeling.During the experiment,the body weight,food intake,excitability,hair color and other general morphology of mice in each group were observed and recorded.Behavioral indexes(Sucrose preference tests and Open Field test)were detected in each group.The levels of 5-hydroxytryptamine(5-HT)and hypothalamic-pituitary-adrenal(HPA)axis hormones,including adrenocorticotropin(ACTH)and corticosterone(CORT),were detected by ELISA.Serum lipid levels,including total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C)and high density lipoprotein cholesterol(HDL-C),were detected by ELISA.HE staining was used to observe the pathological condition of aorta.Results:Compared with blank group,the excitability and food intake of AS+CUMS group were significantly decreased.There were no significant differences in sugar water consumption and activity capacity of mice in AS group,while sugar water consumption and activity capacity of mice in AS+CUMS group were significantly decreased(P<0.01).The serum 5-HT levels in AS group and AS+CUMS group were decreased,and the levels of ACTH and CORT in AS+CUMS group were significantly decreased(P<0.01),and the levels of ACTH and CORT in AS+CUMS group were significantly increased(P<0.01).The serum TC,TG and LDL-C levels of mice in AS group and AS+CUMS group were significantly increased(P<0.01),while the HDL-C level of mice in both groups was significantly decreased(P<0.01).HE staining results showed that the area and degree of plaques in the active vascular lumen of AS group and AS+CUMS group were larger and heavier.Conclusion:High fat feeding combined with CUMS was successful in establishing a mouse model of emotional disorder combined with atherosclerosis.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
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Fund Project:National Natural Science Foundation of China(No.81874415)Liaoning Province Traditional Chinese Medicine Clinical Key Discipline(Specialty)Service Capacity Building Project(No.LNZYXZK.201908)。
文摘Objective:To establish a mouse model of affective disorder complicated with atherosclerosis(AS)by high fat feeding and chronic mild unpredictable stimulation(CUMS),and to provide an animal model for the later study of the prevention and treatment of affective disorder complicated with atherosclerosis by traditional Chinese medicine.Methods:10 C57BL/6J mice were used as blank group,and 20 ApoE-/-mice were randomly divided into AS group and AS+CUMS group.After one week of adaptive feeding,except for the blank group,the other two groups were fed with high fat diet.Meanwhile,the AS+CUMS group was given chronic unpredictable mild stress.The model was evaluated after 16 weeks of modeling.During the experiment,the body weight,food intake,excitability,hair color and other general morphology of mice in each group were observed and recorded.Behavioral indexes(Sucrose preference tests and Open Field test)were detected in each group.The levels of 5-hydroxytryptamine(5-HT)and hypothalamic-pituitary-adrenal(HPA)axis hormones,including adrenocorticotropin(ACTH)and corticosterone(CORT),were detected by ELISA.Serum lipid levels,including total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C)and high density lipoprotein cholesterol(HDL-C),were detected by ELISA.HE staining was used to observe the pathological condition of aorta.Results:Compared with blank group,the excitability and food intake of AS+CUMS group were significantly decreased.There were no significant differences in sugar water consumption and activity capacity of mice in AS group,while sugar water consumption and activity capacity of mice in AS+CUMS group were significantly decreased(P<0.01).The serum 5-HT levels in AS group and AS+CUMS group were decreased,and the levels of ACTH and CORT in AS+CUMS group were significantly decreased(P<0.01),and the levels of ACTH and CORT in AS+CUMS group were significantly increased(P<0.01).The serum TC,TG and LDL-C levels of mice in AS group and AS+CUMS group were significantly increased(P<0.01),while the HDL-C level of mice in both groups was significantly decreased(P<0.01).HE staining results showed that the area and degree of plaques in the active vascular lumen of AS group and AS+CUMS group were larger and heavier.Conclusion:High fat feeding combined with CUMS was successful in establishing a mouse model of emotional disorder combined with atherosclerosis.
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。
