Abstract
BackgroundMajor depressive disorder is a leading cause of disability worldwide, affecting up to 17 % of the general population. The neural mechanisms of depression, however, are yet to be uncovered. Recently, attention has been drawn to the effects of dysfunctional brain-gut axis on depression, and many substances have been suggested to be involved in the communication between the gut and brain, such as ghrelin.MethodsWe herein systematically examined the changes of metabolomics after unpredictable chronic mild stress (UCMS)–induced depression-like behaviors in rats and compared the altered metabolites in the hippocampus and jejunum samples.ResultsOur results show that many metabolites significantly changed with UCMS both in the hippocampus and jejunum, such as L-glutamine, L-tyrosine, hydroxylamine, and 3-phosphoglyceric acid. Further studies suggested that these changes are the reasons for anxiety-like behaviors and depression-like behaviors in UCMS rats and also are the reasons for hippocampal neural plasticity.ConclusionsCoexistence of brain and gut metabolic changes in UCMS-induced depressive behavior in rats suggests a possible role of brain-gut axis in depression. This study provides insights into the neurobiology of depression.
Highlights
To determine if unpredictable chronic mild stress (UCMS) could successfully induce depression-like behaviors, we measured behavior changes, body weight, and plasma corticosterone (CORT) concentration of the rats after the UCMS training
The results showed that UCMS significantly decreased the sucrose consumption in the sucrose preference test (SPT) (p < 0.01, compared with UCMS group; p < 0.01, compared with control group, one-way ANOVA, n=12, Fig. 1A)
Our results showed that UCMS significantly decreased body weight and increased the CORT, which is consistent with our previous reports (Fig. 1E, F) (Gu et al 2018a, b)
Summary
Major depression is affecting more than 17% of populations worldwide (Otte et al 2016; Putnam et al 2017), and the World Health Organization anticipated that depression will become the first health problem in 2020 (Gu, et al 2020). Attention has been drawn to the brain-gut axis, and Qiuyue Xu, Mingchen Jiang and Simeng Gu contributed to this work. The brain-gut axis is a bidirectional, multifaceted communication system (Cryan et al 2019), and the gut and brain might affect each other via the enteric nervous system, the parasympathetic system, the immune system, and microbial metabolites (Duman et al 2016). Major depressive disorder is a leading cause of disability worldwide, affecting up to 17 % of the general population. Attention has been drawn to the effects of dysfunctional brain-gut axis on depression, and many substances have been suggested to be involved in the communication between the gut and brain, such as ghrelin
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