Single cell transcriptomics reveals opioid usage evokes widespread suppression of antiviral gene program
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE128879 | GEO | 2020/04/12
REPOSITORIES: GEO
Similar Datasets
Project description:Chronic opioid usage not only causes addiction behavior through the central nervous system, but also modulates the peripheral immune system. However, how opioid impacts the immune system is still barely characterized systematically. In order to understand the immune modulatory effect of opioids in an unbiased way, here we perform single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells from opioid-dependent individuals and controls to show that chronic opioid usage evokes widespread suppression of antiviral gene program in naive monocytes, as well as in multiple immune cell types upon stimulation with the pathogen component lipopolysaccharide. Furthermore, scRNA-seq reveals the same phenomenon after a short in vitro morphine treatment. These findings indicate that both acute and chronic opioid exposure may be harmful to our immune system by suppressing the antiviral gene program. Our results suggest that further characterization of the immune modulatory effects of opioid is critical to ensure the safety of clinical opioids.
| S-EPMC7250875 | biostudies-literature
Project description:Single cell transcriptomics reveals opioid usage evokes widespread suppression of antiviral gene program
| PRJNA529204 | ENA
Project description:To study the relationship between microRNAs and μ-opioid receptor (MOR) signaling, we examined microRNA expression after chronic morphine or fentanyl treatment in rat primary hippocampal neurons and in mouse hippocampus. Mouse cerebellum region was also tested as a negative control to eliminate microRNA expression changes unrelated to MOR signaling, as the cerebellum is essentially devoid of MOR. We identified a number of microRNAs that altered their expression upon treatment with both morphine and fentanyl in the rat and mouse systems. There were, however, some microRNAs that changed in response to morphine, or fentanyl, but not both. Keywords: Expression profiling There are up to three biological replicates (indicated by 1, 2, and 3) of primary hippocampal neurons from new born rats and the cerebellum and hippocampus regions from adult mice treated for three days (control, morphine, and fentanyl). The biological replicates were from experiments performed on different dates. Each biological replicate contained cells or tissues collected from multiple animals so that enough RNA could be extracted for RNA analysis. RNA was labelled with a green dye, mixed with a reference DNA sample labelled with a red dye. The reference DNA contained a number of synthetic DNA oligos with mature microRNA sequences that served to verify microarray hybridization. RNA signals were in ch1, DNA signals ch2.
2010-05-19 | E-GEOD-14268 | biostudies-arrayexpress
Project description:We examined morphine responsing miRNAs in Zebrafish embroys. Microarray studies revealed morphine can change microRNA expression in Zebrafish embroys.
2010-12-01 | GSE18847 | GEO
Project description:Morphine and its pharmacological derivatives are the most prescribed analgesics for moderate to severe pain management. However, chronic use of morphine reduces pathogen clearance and induces bacterial translocation across the gut barrier. The enteric microbiome has been shown to play a critical role in the preservation of the mucosal barrier function and metabolic homeostasis. Here, we show for the first time, using bacterial 16s rDNA sequencing, that chronic morphine treatment significantly alters the gut microbial composition and induces preferential expansion of the gram-positive pathogenic and reduction of bile-deconjugating bacterial strains. A significant reduction in both primary and secondary bile acid levels was seen in the gut, but not in the liver with morphine treatment. Morphine induced microbial dysbiosis and gut barrier disruption was rescued by transplanting placebo-treated microbiota into morphine-treated animals, indicating that microbiome modulation could be exploited as a therapeutic strategy for patients using morphine for pain management. In this study, we establish a link between the two phenomena, namely gut barrier compromise and dysregulated bile acid metabolism. We show for the first time that morphine fosters significant gut microbial dysbiosis and disrupts cholesterol/bile acid metabolism. Changes in the gut microbial composition is strongly correlated to disruption in host inflammatory homeostasis13,14 and in many diseases (e.g. cancer/HIV infection), persistent inflammation is known to aid and promote the progression of the primary morbidity. We show here that chronic morphine, gut microbial dysbiosis, disruption of cholesterol/bile acid metabolism and gut inflammation; have a linear correlation. This opens up the prospect of devising minimally invasive adjunct treatment strategies involving microbiome and bile acid modulation and thus bringing down morphine-mediated inflammation in the host.
2016-06-01 | E-MTAB-3722 | biostudies-arrayexpress
Project description:Regulator of G protein signaling z1 (RGSz1), a member of the RGS family of proteins, is present in several networks expressing mu opioid receptors (MOPR). By using genetic mouse models for global or brain region-targeted manipulations of RGSz1 expression, we demonstrate that the suppression of RGSz1 function increases the analgesic efficacy of MOPR agonists in male and female mice and delays the development of morphine tolerance while decreasing the sensitivity to rewarding and locomotor activating effects. Using biochemical assays and next-generation RNA sequencing, we identified a key role of RGSz1 in the periaqueductal gray (PAG) in morphine tolerance. Chronic morphine administration promotes RGSz1 activity in the PAG, which in turn modulates transcription mediated by the Wnt/β-catenin signaling pathway to promote analgesic tolerance to morphine. Conversely, the suppression of RGSz1 function stabilizes Axin2-Gaz complexes near the membrane and promotes β-catenin activation, thereby delaying the development of analgesic tolerance. These data show that the regulation of RGS complexes, particularly those involving RGSz1-Gaz, represents a promising target for optimizing the analgesic actions of opioids without increasing the risk of dependence or addiction.
2018-01-12 | GSE109165 | GEO
Project description:To study the relationship between microRNAs and μ-opioid receptor (MOR) signaling, we examined microRNA expression after chronic morphine or fentanyl treatment in rat primary hippocampal neurons and in mouse hippocampus. Mouse cerebellum region was also tested as a negative control to eliminate microRNA expression changes unrelated to MOR signaling, as the cerebellum is essentially devoid of MOR. We identified a number of microRNAs that altered their expression upon treatment with both morphine and fentanyl in the rat and mouse systems. There were, however, some microRNAs that changed in response to morphine, or fentanyl, but not both. Keywords: Expression profiling
2009-05-04 | GSE14268 | GEO
Project description:Opioids analgesics are frequently prescribed in the United States and worldwide. However, serious side effects such as addiction, immunosuppression and gastrointestinal symptoms limit their use. It has been recently demonstrated that morphine treatment results in significant disruption in gut barrier function leading to increased translocation of gut commensal bacteria. Further study indicated distinct alterations in the gut microbiome and metabolome following morphine treatment, contributing to the negative consequences associated with opioid use. However, it is unclear how opioids modulate gut homeostasis in the context of a hospital acquired bacterial infection. In the current study, a mouse model of C. rodentium infection was used to investigate the role of morphine in the modulation of gut homeostasis in the context of a hospital acquired bacterial infection. Citrobacter rodentium is a natural mouse pathogen that models intestinal infection by enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) and causes attaching and effacing lesions and colonic hyperplasia. Morphine treatment resulted in 1) the promotion of C. rodentium systemic dissemination, 2) increase in virulence factors expression with C. rodentium colonization in intestinal contents, 3) altered gut microbiome, 4) damaged integrity of gut epithelial barrier function, 5) inhibition of C. rodentium-induced increase in goblet cells, and 6) dysregulated IL-17A immune response. This is the first study to demonstrate that morphine promotes pathogen dissemination in the context of intestinal C. rodentium infection, indicating morphine modulates virulence factor-mediated adhesion of pathogenic bacteria and induces disruption of mucosal host defense during C. rodentium intestinal infection in mice. This study demonstrates and further validates a positive correlation between opioid drug use/abuse and increased risk of infections, suggesting over-prescription of opioids may increase the risk in the emergence of pathogenic strains and should be used cautiously. Therapeutics directed at maintaining gut homeostasis during opioid use may reduce the comorbidities associated with opioid use for pain management.
2020-02-18 | E-MTAB-7503 | biostudies-arrayexpress
Project description:Endocannabinoids can act as retrograde messengers that allow postsynaptic cells to regulate the strength of their synaptic inputs. In the cerebellum, Purkinje cells (PCs) release endocannabinoids through two mechanisms. Synaptic activation evokes local endocannabinoid release that relies on a pathway that involves the metabotropic glutamate receptor mGluR1 and phospholipase-C (PLC). In contrast, depolarization evokes endocannabinoid release from the entire dendritic arbor. This leads to depolarization-induced suppression of inhibitory (DSI) and excitatory (DSE) synapses by a mechanism that does not involve mGluR1 or PLC. This latter mechanism of endocannabinoid release has only been observed under artificial conditions that transiently elevate postsynaptic calcium to >5 microm. Here, we tested the possibility that this mechanism could lead to retrograde inhibition in response to more realistic calcium signals. At both climbing fiber and inhibitory synapses onto PCs, we found that prolonging the elevation of calcium significantly lowered the peak calcium required to evoke PLC-independent endocannabinoid release. This suggests that the mechanism of endocannabinoid release involved in DSI and DSE is likely to evoke endocannabinoid release in response to physiologically relevant levels of calcium. When dendritic calcium was elevated to 0.4-1 microm for 15 s or more, endocannabinoid release from PCs selectively suppressed inhibitory synapses. This suggests that inhibitory synapses are more sensitive to prolonged calcium increases. Thus, in contrast to localized retrograde inhibition evoked by synaptic activation, modest but sustained calcium elevation could globally suppress inhibitory synapses onto PCs.
| S-EPMC6673843 | biostudies-literature
Project description:Chronic opioid treatment elicits hyperalgesia in mice that is significantly augmented by a human migraine trigger and reduced with migraine therapy. The purpose of this study was to profile mRNA levels (transcriptome) to understand the differences between opioid (morphine) and vehicle treatments in two nervous system regions, the trigeminal ganglia and the nucleus accumbens. Mice received 10 mL/kg intraperitoneal injections of either morphine or vehicle volume twice daily (s.c.) for 4 days where on days 1-3 the dose of morphine was 20 mg/kg, and on day 4 it was 40 mg/kg.
2020-04-14 | GSE126662 | GEO