Explore the vast range of titles available.

Gut microbiota is associated with anxiety and depression, while exercise has been proved to alleviate depressive symptoms. However, the interaction of exercise, depression, and gut microbiota remains unclear. Male C57/BL6J mice were exposed to chronic unpredictable mild stress (CUMS) for 6 weeks and then were subjected to a 5-week swimming program. Behavioral tests, including sucrose preference test (SPT), open field test (OFT), elevated plus-maze (EPM) test, and tail suspension test (TST), were conducted to assess the anxiety-like and depressive behaviors. Gut microbiota analysis was carried out after sample collection. This study showed that CUMS induced depressive behaviors, but swimming exercise increased sucrose preference rate in the SPT, increased time in the center and number of rearing in the OFT, decreased time in the closed arm and increased time in the open arm in EPM, and decreased immobility time in the TST. Firmicutes were the predominant phylum in the gut microbiome, followed by the phyla Bacteroidetes and Proteobacteria. We further found that CUMS and swimming influenced the relative abundance of the genus Desulfovibrio, genus Streptococcus, genus p-75-a5. Among the metabolic pathways, aromatic biogenic amine degradation (PWY-7431), mono-trans and polycis decaprenyl phosphate biosynthesis (PWY-6383), chlorosalicylate degradation (PWY-6107), mycothiol biosynthesis (PWY1G-0), mycolyl-arabinogalactan-peptidoglycan complex biosynthesis (PWY-6397), toluene degradation I (aerobic) (via o-cresol) (PWY-5180), toluene degradation II (aerobic) (via 4-methylcatechol) (PWY-5182), and starch degradation III (PWY-6731) may be related to the mechanism of anti-depression effect. Swimming exercise reverses CUMS-induced depressive behaviors, and the alteration of gut microbiota composition and regulation of microbiota metabolic pathways are involved.

Background Chronic unpredictable mild stress (CUMS) can not only lead to depression-like behavior but also change the composition of the gut microbiome. Regulating the gut microbiome can have an antidepressant effect, but the mechanism by which it improves depressive symptoms is not clear. Short-chain fatty acids (SCFAs) are small molecular compounds produced by the fermentation of non-digestible carbohydrates. SFCAs are ubiquitous in intestinal endocrine and immune cells, making them important mediators of gut microbiome-regulated body functions. The balance between the pro- and anti-inflammatory microglia plays an important role in the occurrence and treatment of depression caused by chronic stress. Non-absorbable antibiotic rifaximin can regulate the structure of the gut microbiome. We hypothesized that rifaximin protects against stress-induced inflammation and depression-like behaviors by regulating the abundance of fecal microbial metabolites and the microglial functions. Methods We administered 150 mg/kg rifaximin intragastrically to rats exposed to CUMS for 4 weeks and investigated the composition of the fecal microbiome, the content of short-chain fatty acids in the serum and brain, the functional profiles of microglia and hippocampal neurogenesis. Results Our results show that rifaximin ameliorated depressive-like behavior induced by CUMS, as reflected by sucrose preference, the open field test and the Morris water maze. Rifaximin increased the relative abundance of Ruminococcaceae and Lachnospiraceae, which were significantly positively correlated with the high level of butyrate in the brain. Rifaximin increased the content of anti-inflammatory factors released by microglia, and prevented the neurogenic abnormalities caused by CUMS. Conclusions These results suggest that rifaximin can regulate the inflammatory function of microglia and play a protective role in pubertal neurodevelopment during CUMS by regulating the gut microbiome and short-chain fatty acids.

Background The microbiota–gut–brain axis plays an important role in the development of depression. The aim of this study was to investigate the effects of 5-HT on cognitive function, learning and memory induced by chronic unforeseeable mild stress stimulation (CUMS) in female mice. CUMS mice and TPH2 KO mice were used in the study. Lactococcus lactis E001-B-8 fungus powder was orally administered to mice with CUMS. Methods We used the open field test, Morris water maze, tail suspension test and sucrose preference test to examine learning-related behaviours. In addition, AB-PAS staining, immunofluorescence, ELISA, qPCR, Western blotting and microbial sequencing were employed to address our hypotheses. Results The effect of CUMS was more obvious in female mice than in male mice. Compared with female CUMS mice, extracellular serotonin levels in TPH2 KO CUMS mice were significantly reduced, and cognitive dysfunction was aggravated. Increased hippocampal autophagy levels, decreased neurotransmitter levels, reduced oxidative stress damage, increased neuroinflammatory responses and disrupted gut flora were observed. Moreover, L. lactis E001-B-8 significantly improved the cognitive behaviour of mice. Conclusions These results strongly suggest that L. lactis E001-B-8 but not FLX can alleviate rodent depressive and anxiety-like behaviours in response to CUMS, which is associated with the improvement of 5-HT metabolism and modulation of the gut microbiome composition.

Microglia activation, increased IL-6 and decreased TGF-β were found in depressed patients or in animal models of depression. IL-6 enhances T helper 17 cell differentiation, thereby causing an imbalance between Th17 and Treg cells, which induces neuroinflammation and neuronal dysfunction. However, whether imbalances between IL-6 and TGF-β and between Th17 and Treg occur in depression and whether depression can be improved upon restoring these imbalances are unknown. Treg promoter IL-2 (1500UI/0.1 mL/day) was used to treat a mouse model of depression induced by chronic unpredictable mild stress (CUMS). The behavior and concentrations of IL-6, TGF-β, Th17, IL-17A, IL-17Rc, Treg-related factors (helios and STAT5), astrocyte A1 phenotype S100β, microglia M1 phenotype Iba-1, indoleamine-2,3-dioxygenase (IDO) enzyme, corticosterone (CORT) and neurotransmitters were evaluated. When compared to controls, CUMS reduced sucrose preference, the number of entries into and the time spent in the open arms of the elevated plus maze and the exploration in the “open field”, while it increased the immobility time in tail suspension, which was ameliorated by IL-2 treatment. RoRα, S100β, IL-17A, IL-17Rc, IL-6, Iba-1, IDO enzyme and CORT concentrations were significantly increased, and Helios, FoxP3+, STAT5 and TGF-β were significantly decreased by CUMS, which were significantly attenuated by IL-2 when compared to the CUMS group. The NE, DA and 5-HT contents and those of their metabolites were decreased by CUMS, which returned to control levels after IL-2 treatment. The study demonstrated that imbalances between IL-6 and TGF-β and between Th17and Treg occurred in the hippocampus of the depression model. IL-2 attenuated depression- and anxiety-like behaviors and normalized the neurotransmitter concentration and the activity of the IDO enzyme, astrocytes and microglia through restoring both balances, but it did not decrease the CORT concentration.

Accumulating evidence has suggested that the gut microbiome plays an important role in depression. Akkermansia muciniphila (AKK), a next-generation probiotic, shows a beneficial effect on immune and metabolic homeostasis. The relative abundance of AKK was found negatively correlated with depressive symptoms in both clinical and pre-clinical studies. To evaluate the potential antidepressant effect of AKK and explore the possible mechanism, we used chronic alcohol exposure and chronic unpredictable mild stress (CUMS) to induce depressive-like behaviors in mice. We found that oral AKK administration significantly reduced the immobility time in the force swimming test (FST) and tail suspension test (TST) in the mice with chronic alcohol exposure and the CUMS mice. The sucrose preference in the mice receiving AKK was significantly increased in the sucrose preference test (SPT). More importantly, AKK implantation significantly increased the level of 5-HT in the gut and PFC of both the alcohol exposure mice and the CUMS mice. Furthermore, AKK had inhibited the expression of SERT in the gut but not in the brain for both NIAAA and the CUMS model mice. Interestingly, the expression of cFos in enteric nerves in the gut significantly decreased after AKK administration. In conclusion, our study demonstrated the antidepressant effect of AKK in mice exposed to alcohol exposure and CUMS, with the potential mechanism that AKK implantation might lead to an increased level of 5-HT and inhibited SERT expression in the gut, and might alter the gut-to-brain signal through suppression of enteric nerves activation.

The brain is the central organ of adaptation to stress because it perceives and determines threats that induce behavioral, physiological, and molecular responses. In humans, chronic stress manifests as an enduring consistent feeling of pressure and being overwhelmed for an extended duration. This can result in a persistent proinflammatory response in the peripheral and central nervous system (CNS), resulting in cellular, physiological, and behavioral effects. Compounding stressors may increase the risk of chronic-stress-induced inflammation, which can yield serious health consequences, including mental health disorders. This review summarizes the current knowledge surrounding the neuroinflammatory response in rodent models of chronic stress—a relationship that is continually being defined. Many studies investigating the effects of chronic stress on neuroinflammation in rodent models have identified significant changes in inflammatory modulators, including nuclear factor-κB (NF-κB) and toll-like receptors (TLRs), and cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and IL-6. This suggests that these are key inflammatory factors in the chronic stress response, which may contribute to the establishment of anxiety and depression-like symptoms. The behavioral and neurological effects of modulating inflammatory factors through gene knockdown (KD) and knockout (KO), and conventional and alternative medicine approaches, are discussed.

In recent years, depression has become a global public health concern, and one of the common concomitant symptoms are diminished sexual motivation and impaired sexual performance. The aim of this study was to investigate the potential effects of oligosaccharides (MOO) on depression and its concomitant symptom, sexual dysfunction. Chronic unpredictable mild stress (CUMS)-induced depression model was constructed, and the effects of MOO on depression and sexual abilities were evaluated. The results revealed that MOO was able to alleviate CUMS-induced depression-like behavior in mice, to inhibit hippocampal neuron apoptosis, to reverse monoamine neurotransmitter imbalance, increase Brain-derived neurotrophic factor (BDNF) expression levels in the hippocampus, to modulate the composition and distribution of gut microbiota, and to increase the abundance of probiotics after continuous gavage of MOO for 28 days. MOO further confirmed that sexual dysfunction is closely related to the development of depression by improving the lack of sexual motivation and low sexual performance in CUMS-induced depressed mice, modulating the disruption of sex hormone secretion in serum, and alleviating sperm morphology and functional defects in the epididymis. These findings on MOO provide a basis for exploring its antidepressant mechanism, its use to improve hypogonadotropic symptoms, and for future development of new antidepressant drug to improves hypogonadotropic symptoms.

Rationale and objectivePaeoniflorin has been reported to exhibit antidepressant-like effects in several animal model depression; and it also exerts a neuroprotective effect. In the present study, we investigated the effects of paeoniflorin administration on depression-like behaviors and cognitive abilities in mice subjected to chronic unpredictable mild stress (CUMS), an animal model associated with depressive disorders and cognitive deficits.MethodsWe administered paeoniflorin (20 mg/kg), which is the main active constituent extracted from Paeonia lactiflora Pall. and exerts multiple pharmacological actions, to CUMS mice. Subsequently, animals were subjected to tests of depression-like behavior including the sucrose preference test, the forced swimming test and the tail suspension test. The Morris water maze (MWM) task was applied to evaluate learning and memory capacity. Hippocampal CA1 long-term potentiation (LTP) was recorded. Dendritic spine density and the expression levels of brain-derived neurotrophic factor (BDNF) and postsynaptic density protein 95 (PSD95) in the hippocampus were also investigated.ResultsThe administration of paeoniflorin protected against CUMS-induced depression-like behavior. Paeoniflorin also improved the performance of CUMS mice in the MWM. The impairment of hippocampal CA1 LTP caused by CUMS was also reversed. Furthermore, paeoniflorin administration prevented decreases in dendritic spine density and in the expression of BDNF and PSD95 in the hippocampus of CUMS mice.ConclusionOur observations suggest that paeoniflorin is a potential antidepressant that protects against cognitive impairment in depression.

Depression is a common but serious mental illness; meanwhile, it is also an inflammatory disorder. Toll-like receptor 4 (TLR4), as the pattern recognition receptor, has been shown to play a vital role in neuroinflammation. The nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome acts as an important signaling molecule downstream of TLR4 and can promote the maturation of inflammatory cytokines, such as interleukin-1β (IL-1β). Tetramethylpyrazine (TMP) is a natural compound with neuroprotective effects but with unknown mechanisms on its antidepressant-like effect. In this study, we hypothesized that TMP ameliorates depression may be through the inhibition of the TLR4-NF-κB-NLRP3 signal pathway. Our results have shown that chronic unpredictable mild stress (CUMS) that induced the decreased sucrose preference and increased immobile time was prominently reversed by TMP and fluoxetine. Additionally, we also found that CUMS induced the upregulation of proinflammatory cytokines; TLR4 and NLRP3-associated proteins were significantly suppressed by TMP in the prefrontal cortex and hippocampus. TMP also exhibited potent antioxidant effects and increased the monoamine levels in the serum and brain, such as increasing the activity of SOD and GSH-Px, and reducing the activity of MDA in the serum, and elevating the 5-HT and NE concentration in the serum and brain. Moreover, treatment with Cli-095 (TLR4 inhibitor) also markedly inhibited CUMS-induced depression-like behaviors. Taken together, our findings suggested that TMP exerted a potential antidepressant-like effect in CUMS mice, and the molecular mechanisms may relate to inhibit the TLR4-NF-κB-NLRP3 signaling pathway in the brain.