Dataset Information

The Ameliorative Effects of Isorhynchophylline on Morphine Dependence Are Mediated Through the Microbiota-Gut-Brain Axis.

ABSTRACT: Morphine abuse is a global public health problem. Increasing evidence has shown that gut microbiota dysbiosis plays an important role in several central nervous system diseases. However, whether there is an association between gut microbiota and morphine dependence remains unclear. In this study, the effects of isorhynchophylline on morphine dependence were evaluated based on the microbiota-gut-brain axis (MGBA). The results showed that isorhynchophylline could reverse the changes in alpha and beta diversity, composition, and richness of the intestinal flora occurring in morphine-dependent zebrafish, as well as the morphine-induced changes in the expression of MGBA-related genes in BV2 cells and the brain and intestine of zebrafish. Based on the results, we then used antibiotics to evaluate whether disrupting the gut microbiota would affect morphine addiction in zebrafish. The results showed that the antibiotic-induced intestinal floral imbalance changed the behavior of morphine-dependent zebrafish, the characteristics of the zebrafish intestinal flora, and the expression of MGBA-related genes in the zebrafish brain and intestine. Importantly, we also show that, following antibiotic administration, the ameliorative effects of isorhynchophylline on morphine addiction were lost. Together, our results indicate that the gut microbiota interacts with the brain, and dysbiosis of the intestinal flora may affect the efficacy of isorhynchophylline in the body. Our findings provide a novel framework for understanding the mechanisms of morphine addiction through the MGBA and may provide new therapeutic strategies for the use of Chinese medicines in the prevention of drug addiction.

SUBMITTER: Chen Z

PROVIDER: S-EPMC8218633 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundAtrial natriuretic peptide (ANP) secreted from atrial myocytes is shown to possess anti-inflammatory, anti-oxidant and immunomodulatory effects. The aim of this study is to assess the effect of ANP on bacterial lipopolysaccharide (LPS)-induced endotoxemia-derived neuroinflammation and cognitive impairment.MethodsLPS (5 mg/kg) was given intraperitoneally to mice. Recombinant human ANP (rhANP) (1.0 mg/kg) was injected intravenously 24 h before and/or 10 min after LPS injection. Subdiaphragmatic vagotomy (SDV) was performed 14 days before LPS injection or 28 days before fecal microbiota transplantation (FMT). ANA-12 (0.5 mg/kg) was administrated intraperitoneally 30 min prior to rhANP treatment.ResultsLPS (5.0 mg/kg) induced remarkable splenomegaly and an increase in the plasma cytokines at 24 h after LPS injection. There were positive correlations between spleen weight and plasma cytokines levels. LPS also led to increased protein levels of ionized calcium-binding adaptor molecule (iba)-1, cytokines and inducible nitric oxide synthase (iNOS) in the hippocampus. LPS impaired the natural and learned behavior, as demonstrated by an increase in the latency to eat the food in the buried food test and a decrease in the number of entries and duration in the novel arm in the Y maze test. Combined prophylactic and therapeutic treatment with rhANP reversed LPS-induced splenomegaly, hippocampal and peripheral inflammation as well as cognitive impairment. However, rhANP could not further enhance the protective effects of SDV on hippocampal and peripheral inflammation. We further found that PGF mice transplanted with fecal bacteria from rhANP-treated endotoxemia mice alleviated the decreased protein levels of hippocampal polyclonal phosphorylated tyrosine kinase receptor B (p-TrkB), brain-derived neurotrophic factor (BDNF) and cognitive impairment, which was abolished by SDV. Moreover, TrkB/BDNF signaling inhibitor ANA-12 abolished the improving effects of rhANP on LPS-induced cognitive impairment.ConclusionsOur results suggest that rhANP could mitigate LPS-induced hippocampal inflammation and cognitive dysfunction through subdiaphragmatic vagus nerve-mediated gut microbiota-brain axis.

Project description:BackgroundParkinson's disease (PD) is a prevalent neurodegenerative disorder, displaying not only well-known motor deficits but also gastrointestinal dysfunctions. Consistently, it has been increasingly evident that gut microbiota affects the communication between the gut and the brain in PD pathogenesis, known as the microbiota-gut-brain axis. As an approach to re-establishing a normal microbiota community, fecal microbiota transplantation (FMT) has exerted beneficial effects on PD in recent studies. Here, in this study, we established a chronic rotenone-induced PD mouse model to evaluate the protective effects of FMT treatment on PD and to explore the underlying mechanisms, which also proves the involvement of gut microbiota dysbiosis in PD pathogenesis via the microbiota-gut-brain axis.ResultsWe demonstrated that gut microbiota dysbiosis induced by rotenone administration caused gastrointestinal function impairment and poor behavioral performances in the PD mice. Moreover, 16S RNA sequencing identified the increase of bacterial genera Akkermansia and Desulfovibrio in fecal samples of rotenone-induced mice. By contrast, FMT treatment remarkably restored the gut microbial community, thus ameliorating the gastrointestinal dysfunctions and the motor deficits of the PD mice. Further experiments revealed that FMT administration alleviated intestinal inflammation and barrier destruction, thus reducing the levels of systemic inflammation. Subsequently, FMT treatment attenuated blood-brain barrier (BBB) impairment and suppressed neuroinflammation in the substantia nigra (SN), which further decreased the damage of dopaminergic neurons. Additional mechanistic investigation discovered that FMT treatment reduced lipopolysaccharide (LPS) levels in the colon, the serum, and the SN, thereafter suppressing the TLR4/MyD88/NF-κB signaling pathway and its downstream pro-inflammatory products both in the SN and the colon.ConclusionsOur current study demonstrates that FMT treatment can correct the gut microbiota dysbiosis and ameliorate the rotenone-induced PD mouse model, in which suppression of the inflammation mediated by the LPS-TLR4 signaling pathway both in the gut and the brain possibly plays a significant role. Further, we prove that rotenone-induced microbiota dysbiosis is involved in the genesis of PD via the microbiota-gut-brain axis. Video abstract.

Dataset Information

The Ameliorative Effects of Isorhynchophylline on Morphine Dependence Are Mediated Through the Microbiota-Gut-Brain Axis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets