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Updated: Aug 16, 2026
The Unpredictable Chronic Mild Stress Protocol for Inducing Anhedonia in Mice
Published on: October 24, 2018
CUMS and dexamethasone induce depression-like phenotypes in mice by differentially altering gut microbiota and
Jing Wu1, Jinhang Li1, Chhetri Gaurav1
1School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
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 both α and β diversity. 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-1β in 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.
