Background Although the link between gut microbiota and depression has been suggested,changes of gut microbiota vary largely among individuals with depression.Aims Explore the heterogeneity of microbiota-gut-brain axi...Background Although the link between gut microbiota and depression has been suggested,changes of gut microbiota vary largely among individuals with depression.Aims Explore the heterogeneity of microbiota-gut-brain axis and new pathogenic characteristics in murine models of depression.Methods Adolescent female mice were randomly divided into control(CON)group(n=10),chronic unexpected mild stress(CUMS)group(n=15)and dexamethasone(DEX)group(n=15).Mice in the DEX group were gavaged twice a day with 0.2 mg/kg of DEX for 5 weeks,whereas CON mice were given the same amount of solvent.Mice in the CUMS group were exposed to stressors.After behavioural evaluations,all mice were sacrificed for harvesting tissues and blood samples.Enzyme-linked immunosorbent assay(ELISA)was conducted for measuring levels of corticosterone(CORT)and interleukin-1β(IL-1β)in sera,whereas levels of protein expression in colon and hippocampal tissues were examined by western blot.Faecal microbial communities were analysed by sequencing 16S rDNAs.Results Mice in CUMS and DEX groups exhibited severe depression-like behaviours.Compared with CON mice,CUMS-exposed mice showed a significant increase in bothαandβdiversity.Prevotellaceae and Desulfovibrio were enriched,whereas Bacilli were decreased in the faeces of mice in the CUMS group.DEX-treated mice had a decrease in the abundance of Clostridium XVIII.Levels of occludin in colon tissue of DEX-treated mice were reduced.Relative to mice in the CON and CUMS groups,DEX-treated mice contained higher serum levels of CORT and IL-1β.Compared with CON mice,mice in the DEX and CUMS groups had higher levels of IL-1βin sera and lower levels of glial fibrillary acidic protein(GFAP),Nestin,Synapsin-1 and P2Y12 receptor in the hippocampus.Conclusions Changes of gut microbiota diversity,intestinal integrity and neuroinflammation in the brain contribute to CUMS-induced depression,whereas pathobionts and excessive immunosuppression with damaged neuronal synapses is a basis of the DEX-induced depression.展开更多
Objective:To investigate the effect of Fuhe decoction on the behavior and levels of monoamine neurotransmitters in different brain regions in a depression rat model induced by chronic unpredictable mild stimulation(CU...Objective:To investigate the effect of Fuhe decoction on the behavior and levels of monoamine neurotransmitters in different brain regions in a depression rat model induced by chronic unpredictable mild stimulation(CUMS)combined with social isolation.Methods:Fifty male SD rats were randomly divided into a blank group,model group,fluoxetine group,Chaiqinwendan decoction group,and Fuhe decoction group.Chronic unpredictable mild stimulation combined with a social isolation method was used to replicate the depression rat model.After 42 days of administration,a tail suspension test and high-performance liquid electrochemical detection(HPLC-ECD)were used to detect the behavioral changes and changes in the content of monoamine neurotransmitters norepinephrine(NE),dopamine(DA),5-hydroxytrytamine(5-HT),and metabolites in different brain regions of rats in each group before and after treatment.Results:Compared with the model group,the epinephrine(E)content in the Fuhe decoction group was highly significantly increased(P<.01).Compared with the model group,the 5-HT content of the prefrontal cortex in rats in the Fuhe decoction group was highly significantly increased(P<.01).Furthermore,compared with the model group,the 5-HT content in the hippocampus of rats in the Fuhe decoction group was significantly increased(P<.05).Conclusion:Fuhe decoction can improve the depression-like behaviors of model rats,and its antidepressant effect may be related to the increase in 5-HT content in the prefrontal cortex and hippocampus of rats.展开更多
基金This project was supported by the Shanghai Key Laboratory of Psychotic Disorders(NO.13dz2260500)National Natural Science Foundation of China(No.81871122)Interdisciplinary Program of Shanghai Jiao Tong University(ZH2018QNA59).
文摘Background Although the link between gut microbiota and depression has been suggested,changes of gut microbiota vary largely among individuals with depression.Aims Explore the heterogeneity of microbiota-gut-brain axis and new pathogenic characteristics in murine models of depression.Methods Adolescent female mice were randomly divided into control(CON)group(n=10),chronic unexpected mild stress(CUMS)group(n=15)and dexamethasone(DEX)group(n=15).Mice in the DEX group were gavaged twice a day with 0.2 mg/kg of DEX for 5 weeks,whereas CON mice were given the same amount of solvent.Mice in the CUMS group were exposed to stressors.After behavioural evaluations,all mice were sacrificed for harvesting tissues and blood samples.Enzyme-linked immunosorbent assay(ELISA)was conducted for measuring levels of corticosterone(CORT)and interleukin-1β(IL-1β)in sera,whereas levels of protein expression in colon and hippocampal tissues were examined by western blot.Faecal microbial communities were analysed by sequencing 16S rDNAs.Results Mice in CUMS and DEX groups exhibited severe depression-like behaviours.Compared with CON mice,CUMS-exposed mice showed a significant increase in bothαandβdiversity.Prevotellaceae and Desulfovibrio were enriched,whereas Bacilli were decreased in the faeces of mice in the CUMS group.DEX-treated mice had a decrease in the abundance of Clostridium XVIII.Levels of occludin in colon tissue of DEX-treated mice were reduced.Relative to mice in the CON and CUMS groups,DEX-treated mice contained higher serum levels of CORT and IL-1β.Compared with CON mice,mice in the DEX and CUMS groups had higher levels of IL-1βin sera and lower levels of glial fibrillary acidic protein(GFAP),Nestin,Synapsin-1 and P2Y12 receptor in the hippocampus.Conclusions Changes of gut microbiota diversity,intestinal integrity and neuroinflammation in the brain contribute to CUMS-induced depression,whereas pathobionts and excessive immunosuppression with damaged neuronal synapses is a basis of the DEX-induced depression.
基金the Foundation of new teachers of Beijing University of Traditional Chinese Medicine(2019-JYB-XJSJJ-001)。
文摘Objective:To investigate the effect of Fuhe decoction on the behavior and levels of monoamine neurotransmitters in different brain regions in a depression rat model induced by chronic unpredictable mild stimulation(CUMS)combined with social isolation.Methods:Fifty male SD rats were randomly divided into a blank group,model group,fluoxetine group,Chaiqinwendan decoction group,and Fuhe decoction group.Chronic unpredictable mild stimulation combined with a social isolation method was used to replicate the depression rat model.After 42 days of administration,a tail suspension test and high-performance liquid electrochemical detection(HPLC-ECD)were used to detect the behavioral changes and changes in the content of monoamine neurotransmitters norepinephrine(NE),dopamine(DA),5-hydroxytrytamine(5-HT),and metabolites in different brain regions of rats in each group before and after treatment.Results:Compared with the model group,the epinephrine(E)content in the Fuhe decoction group was highly significantly increased(P<.01).Compared with the model group,the 5-HT content of the prefrontal cortex in rats in the Fuhe decoction group was highly significantly increased(P<.01).Furthermore,compared with the model group,the 5-HT content in the hippocampus of rats in the Fuhe decoction group was significantly increased(P<.05).Conclusion:Fuhe decoction can improve the depression-like behaviors of model rats,and its antidepressant effect may be related to the increase in 5-HT content in the prefrontal cortex and hippocampus of rats.
