Dataset Information

Melatonin Alleviates Neuroinflammation and Metabolic Disorder in DSS-Induced Depression Rats.

ABSTRACT: There is a bidirectional relationship between inflammatory bowel disease (IBD) and depression/anxiety. Emerging evidences indicate that the liver may be involved in microbiota-gut-brain axis. This experiment focused on the role of melatonin in regulating the gut microbiota and explores its mechanism on dextran sulphate sodium- (DSS-) induced neuroinflammation and liver injury. Long-term DSS-treatment increased lipopolysaccharide (LPS), proinflammation cytokines IL-1? and TNF-?, and gut leak in rats, breaking blood-brain barrier and overactivated astrocytes and microglia. Ultimately, the rats showed depression-like behavior, including reduction of sucrose preference and central time in open field test and elevation of immobility time in a forced swimming test. Oral administration with melatonin alleviated neuroinflammation and depression-like behaviors. However, melatonin supplementation did not decrease the level of LPS but increase short-chain fatty acid (SCFA) production to protect DSS-induced neuroinflammation. Additionally, western blotting analysis suggested that signaling pathways farnesoid X receptor-fibroblast growth factor 15 (FXR-FGF 15) in gut and apoptosis signal-regulating kinase 1 (ASK1) in the liver overactivated in DSS-treated rats, indicating liver metabolic disorder. Supplementation with melatonin markedly inhibited the activation of these two signaling pathways and its downstream p38. As for the gut microbiota, we found that immune response- and SCFA production-related microbiota, like Lactobacillus and Clostridium significantly increased, while bile salt hydrolase activity-related microbiota, like Streptococcus and Enterococcus, significantly decreased after melatonin supplementation. These altered microbiota were consistent with the alleviation of neuroinflammation and metabolic disorder. Taken together, our findings suggest melatonin contributes to reshape gut microbiota and improves inflammatory processes in the hippocampus (HPC) and metabolic disorders in the liver of DSS rats.

SUBMITTER: Lv WJ

PROVIDER: S-EPMC7415091 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Melatonin Alleviates Neuroinflammation and Metabolic Disorder in DSS-Induced Depression Rats.

Lv Wei-Jie WJ Liu Cui C Yu Lin-Zeng LZ Zhou Jia-Hao JH Li Yue Y Xiong Ying Y Guo Ao A Chao Li-Min LM Qu Qian Q Wei Guang-Wei GW Tang Xing-Gang XG Yin Yu-Long YL Guo Shi-Ning SN

Oxidative medicine and cellular longevity 20200730

There is a bidirectional relationship between inflammatory bowel disease (IBD) and depression/anxiety. Emerging evidences indicate that the liver may be involved in microbiota-gut-brain axis. This experiment focused on the role of melatonin in regulating the gut microbiota and explores its mechanism on dextran sulphate sodium- (DSS-) induced neuroinflammation and liver injury. Long-term DSS-treatment increased lipopolysaccharide (LPS), proinflammation cytokines IL-1<i>β</i> and TNF-<i>α</i>, and ...[more]

PMID: 32802257

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Project description:BackgroundDanggui Sini decoction (DSD), a traditional Chinese medicine formula, has the function of nourishing blood, warming meridians, and unblocking collaterals. Our clinical and animal studies had shown that DSD can effectively protect against oxaliplatin (OXA)-induced peripheral neuropathy (OIPN), but the detailed mechanisms remain uncertain. Multiple studies have confirmed that gut microbiota plays a crucial role in the development of OIPN. In this study, the potential mechanism of protective effect of DSD against OIPN by regulating gut microbiota was investigated.MethodsThe neuroprotective effects of DSD against OIPN were examined on a rat model of OIPN by determining mechanical allodynia, biological features of dorsal root ganglia (DRG) as well as proinflammatory indicators. Gut microbiota dysbiosis was characterized using 16S rDNA gene sequencing and metabolism disorders were evaluated using untargeted and targeted metabolomics. Moreover the gut microbiota mediated mechanisms were validated by antibiotic intervention and fecal microbiota transplantation.ResultsDSD treatment significantly alleviated OIPN symptoms by relieving mechanical allodynia, preserving DRG integrity and reducing proinflammatory indicators lipopolysaccharide (LPS), IL-6 and TNF-α. Besides, DSD restored OXA induced intestinal barrier disruption, gut microbiota dysbiosis as well as systemic metabolic disorders. Correlation analysis revealed that DSD increased bacterial genera such as Faecalibaculum, Allobaculum, Dubosiella and Rhodospirillales_unclassified were closely associated with neuroinflammation related metabolites, including positively with short-chain fatty acids (SCFAs) and sphingomyelin (d18:1/16:0), and negatively with pi-methylimidazoleacetic acid, L-glutamine and homovanillic acid. Meanwhile, antibiotic intervention apparently relieved OIPN symptoms. Furthermore, fecal microbiota transplantation further confirmed the mediated effects of gut microbiota.ConclusionDSD alleviates OIPN by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.

Project description:Inflammatory bowel disease (namely, colitis) severely impairs human health. Isoleucine is reported to regulate immune function (such as the production of immunoreactive substances). The aim of this study was to investigate whether l-isoleucine administration might alleviate dextran sulfate sodium (DSS)-induced colitis in rats. In the in vitro trial, IEC-18 cells were treated by 4 mmol/L l-isoleucine for 12 h, which relieved the decrease of cell viability that was induced by TNF-α (10 ng/ml) challenge for 24 h (P <0.05). Then, in the in vivo experiment, a total of 44 Wistar rats were allotted into 2 groups that were fed l-isoleucine-supplemented diet and control diet for 35 d. From 15 to 35 d, half of the rats in the 2 groups drank the 4% DSS-adding water. Average daily gain, average daily feed intake and feed conversion of rats were impaired by DSS challenge (P <0.05). Drinking the DSS-supplementing water also increased disease activity index (DAI) and serum urea nitrogen level (P <0.05), shortened colonic length (P <0.05), impaired colonic enterocyte apoptosis, cell cycle, and the ZO-1 mRNA expression (P <0.05), increased the ratio of CD11c-, CD64-, and CD169-positive cells in colon (P <0.05), and induced extensive ulcer, infiltration of inflammatory cells, and collagenous fiber hyperplasia in colon. However, dietary l-isoleucine supplementation attenuated the negative effect of DSS challenge on growth performance (P <0.05), DAI (P <0.05), colonic length and enterocyte apoptosis (P <0.05), and dysfunction of colonic histology, and downregulated the ratio of CD11c-, CD64-, and CD169-positive cells, pro-inflammation cytokines and the mRNA expression of TLR4, MyD88, and NF-κB in the colon of rats (P <0.05). These results suggest that supplementing l-isoleucine in diet improved the DSS-induced growth stunting and colonic damage in rats, which could be associated with the downregulation of inflammation via regulating TLR4/MyD88/NF-κB pathway in colon.

Project description:Introduction: Major depressive disorder is a mental disease with complex pathogenesis and treatment mechanisms involving changes in both the gut microbiota and neuroinflammation. Cuscutae Semen (CS), also known as Chinese Dodder seed, is a medicinal herb that exerts several pharmacological effects. These include neuroprotection, anti-neuroinflammation, the repair of synaptic damage, and the alleviation of oxidative stress. However, whether CuscutaeSemen exerts an antidepressant effect remains unknown. Methods: In this study, we evaluated the effect of CS on chronic unpredictable stress (CUS)-induced depression-like behaviors in mice by observing changes in several inflammatory markers, including proinflammatory cytokines, inflammatory proteins, and gliocyte activation. Meanwhile, changes in the gut microbiota were analyzed based on 16 S rRNA sequencing results. Moreover, the effect of CS on the synaptic ultrastructure was detected by transmission electron microscopy. Results: We found that the CS extract was rich in chlorogenic acid and hypericin. And CS relieved depression-like behaviors in mice exposed to CUS. Increased levels of cytokines (IL-1β and TNF-α) and inflammatory proteins (NLRP3, NF-κB, and COX-2) induced by CUS were reversed after CS administration. The number of astrocytes and microglia increased after CUS exposure, whereas they decreased after CS treatment. Meanwhile, CS could change the structure of the gut microbiota and increase the relative abundance of Lactobacillus. Moreover, there was a significant relationship between several Lactobacilli and indicators of depression-like behaviors and inflammation. There was a decrease in postsynaptic density after exposure to CUS, and this change was alleviated after CS treatme. Conclusion: This study found that CS treatment ameliorated CUS-induced depression-like behaviors and synaptic structural defects in mice via the gut microbiota-neuroinflammation axis. And chlorogenic acid and hypericin may be the main active substances for CS to exert antidepressant effects.

Dataset Information

Melatonin Alleviates Neuroinflammation and Metabolic Disorder in DSS-Induced Depression Rats.

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Melatonin Alleviates Neuroinflammation and Metabolic Disorder in DSS-Induced Depression Rats.

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