No abstract

These results suggest that ECS can reverse the harmful behavioral effects of CUMS in rats and that the behavioral alterations induced by ECS and/or CUMS may be associated with hippocampal neuroplasticity and SYP levels.

Lipopolysaccharides (LPS) are proinflammation mediators that can induce the inflammatory model of the hippocampal neuron, and neuroinflammation participates in the pathophysiology of depression. Xiaoyao Pill is a classical Chinese medicine formula that has been used for the treatment of mental disorders such as depression in China since the Song dynasty. We established a hippocampal neuronal cell inflammation model by LPS and investigate the intervention effect and mechanism of Xiaoyao Pills. The expression levels of IL-6, TNF-α, IDO, 5-HT, brain-derived neurotrophic factor, and β-nerve growth factor were detected by enzyme-linked immunosorbent assay. mRNA levels of IL-6, TNF-α, 5-HT1A, IDO-1, brain-derived neurotrophic factor, nerve growth factor, tropomyosin receptor kinase B, tropomyosin receptor kinase A, and cAMP response element-binding protein were detected by reverse transcription-polymerase chain reaction. To further validate, protein expression was determined by western blot and immunofluorescence. Lipopolysaccharide-induced neuroinflammatory state resulted in the release of IL-6, TNF-α, and IDO and a decrease of BDNF, NGF, TrkB, TrkA, CREB, p-CREB, p-CREB/CREB, and SYP and inhibited hippocampal neurogenesis in the hippocampal neuron. Xiaoyao Pills significantly decreased the levels of IL-6, TNF-α, and IDO in cell supernatant and increased the expression of BDNF, NGF, TrkB, TrkA, CREB, p-CREB, p-CREB/CREB, and SYP as well as the average optical density of BrdU/NeuN double-labelled positive cells. Our study shows that lipopolysaccharides induce inflammation and nerve damage in hippocampal neurons, which are closely related to the pathological mechanism of depression. Xiaoyao Pills (XYW) play an important neuroprotective effect, which is related to its inhibition of neuronal inflammation and promoting the recovery of nerve injury. These results provide a pharmacologic basis for the treatment of depression of XYW in clinical application.

Glucagon-like peptide-1 (GLP-1) reduces postprandial hyperglycaemia, but its short half-life inhibits clinical application. The aim of the current study was to evaluate the treatment efforts of an engineered strain, Lactobacillus plantarum -pMG36e-GLP-1 ( L. plantarum -pMG36e-GLP-1), that continuously expresses GLP-1 in spontaneous type 2 diabetes mellitus (T2DM) monkeys. After 7 weeks of oral supplementation with L. plantarum -pMG36e-GLP-1, the fasting blood glucose (FPG) of monkeys was significantly (p < 0.05) reduced to a normal level and only a small amount of weight was lost. The results of metagenomic sequencing showed that L. plantarum -pMG36e-GLP-1 caused a substantial (p < 0.05) reduction in the intestinal pathogen Prevotella and marked enhancement of butyrate-producing Alistipes genera. According to the functional analysis using Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways, 19 metabolism-related pathways were significantly enriched in T2DM monkeys after treatment with L. plantarum -pMG36e-GLP-1. LC-MS faecal metabolomics analysis found 41 significant differential metabolites (11 higher and 30 lower) in monkeys after treatment pathways linked to the metabolism of cofactors and vitamins were the most relevant. The present study suggests that L. plantarum -pMG36e-GLP-1 had an impact on the gut microbial composition and faecal metabolomic profile in spontaneous T2DM monkeys and may be a novel candidate for diabetes treatment.

Background. Intestinal microorganisms play an important role in regulating the neurodevelopment and the brain functions of the host through the gut-brain axis. Lactobacillus, one of the most representative intestinal probiotics, produces important effects on human physiological functions. Our previous studies reveal that the Lactobacillus plantarum WLPL04 has a series of beneficial actions, such as antiadhesion of pathogens, protection from the harmful effect of sodium dodecyl sulfate, and anti-inflammatory stress on Caco2 cells. However, its effects on brain functions remain unknown. The present study aims to evaluate the potential effect of L. plantarum WLPL04 on anxiety/depressive-like behaviors in chronically restrained mice. Methods. Newly weaned mice were exposed to chronic restraint stress for four weeks and raised daily with or without L. plantarum WLPL04 water supplement. Animals were behaviorally assessed for anxiety/depression and cognitive functions. The 16S rRNA sequencing was performed to analyze the intestinal microbiota structure. The levels of the medial prefrontal cortical (mPFC) brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) and serum 5-hydroxytryptamine (5-HT) were examined using Western blot and enzyme-linked immunosorbent assay. Results. The chronic stress-induced anxiety/depressive-like behaviors and cognitive deficits were significantly alleviated by the L. plantarum WLPL04 treatment. The 16S rRNA sequencing analysis showed that the chronic stress reduced the diversity and the richness of intestinal microbiota, which were rescued by the L. plantarum WLPL04 treatment. The levels of BDNF and TrkB in the mPFC and the concentration of 5-HT in the serum remained unchanged in chronically restrained mice treated with the L. plantarum WLPL04. Conclusions. The L. plantarum WLPL04 can rescue anxiety/depressive-like behaviors and cognitive dysfunctions, reverse the abnormal change in intestinal microbiota, and alleviate the reduced levels of 5-HT, BDNF, and TrkB induced by chronic stress in mice, providing an experimental basis for the therapeutic application of L. plantarum on anxiety/depression.