Metabolomics changes in brain-gut axis after unpredictable chronic mild stress

Abstract

Background Major 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. Methods We 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. Results Our 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. Conclusions Coexistence 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.

Monoamine Neurotransmitters Control Basic Emotions and Affect Major Depressive Disorders

“…Tremendous progress has been made in studying the bidirectional interactions between the gastrointestinal tract and the central nervous system [ 56 ], and understanding the interaction between the digestive system with the brain may provide novel approaches for prevention and treatment of MDD [ 57 , 58 ]. Indeed, the digestive system has also been found to play an important role in MDD, including liver [ 59 , 60 ] and intestine [ 61 ].…”

The Relationship Between 5-Hydroxytryptamine and Its Metabolite Changes With Post-stroke Depression

“…Furthermore, 5-HT levels can be affected by three neurobiologically related factors of PSD: increased inflammation and trauma, decreased cerebral brain-derived neurotrophic factor (BDNF), and dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis. Raison et al ( 87 ) reported that the metabolisms of 5-HT are affected by the central nervous system (CNS) inflammatory response ( 88 ). A peripherally administered cytokine could activate a CNS inflammatory response in humans that interacted with 5-HT metabolism, which was associated with depression.…”

Editorial: Neurotransmitters and Emotions, Volume II

“…In spite of its central importance for human beings, emotion is still one of the least studied subjects among the life sciences (Gu et al, 2016 ). Even though the last century has witnessed many progresses in emotional studies, psychological analyses have not resolved many of the core issues surrounding emotions (Xu et al, 2022 ), such as the number of basic emotions, and the definition of basic emotions. Although there has been no shortage of psychological research on these debates, for instance, there is little agreement about how many emotions are “basic,” which emotions are “basic,” and why they are “basic” (Liang et al, 2021 ).…”

“…Many scientists started to identify the neural structures that are responsible for particular emotions in the mid-twentieth century, and found that the limbic system might be the brain locus for emtions, and called Papez circuit the emotional brain. These pioneering work outlined the neural anatomical basis of emotion, and helped locate many important structures involved in basic emotions, such as the amygdala, which might be the place for fearful emotions (Xu et al, 2022 ). However, these investigations stopped with the development of behaviorism, which suggested that emotion is not a kind of behavior that can be objectively studied in the laboratory, because of its introspection nature.…”