Epigenome-wide study of brain DNA methylation following acute opioid intoxication
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PROVIDER: PRJNA692166 | ENA |
REPOSITORIES: ENA
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Project description:Opioid abuse poses significant risk to individuals in the United States and epigenetic changes are a leading potential biomarker of opioid abuse. Current evidence, however, is mostly limited to candidate gene analysis in whole blood. Here, we provide Illumina HumanMethylationEPIC array data generated in dorsolateral prefrontal cortex tissue from 153 deceased invidiuals: 72 who died of acute opioid intoxication, 53 psychiatric controls, and 28 normal controls. Using these data, we conducted an epigenome-wide association study and identified one CpG site within a gene (NTN1) that may be related to opioid use. We also detected accelerated PhenoAge in opioid samples compared to control samples.
2021-04-01 | GSE164822 | GEO
Project description:BackgroundOpioid abuse poses significant risk to individuals in the United States and epigenetic changes are a leading potential biomarker of opioid abuse. Current evidence, however, is mostly limited to candidate gene analysis in whole blood. To clarify the association between opioid abuse and DNA methylation, we conducted an epigenome-wide analysis of DNA methylation in brain samples of individuals who died from acute opioid intoxication and group-matched controls.MethodsTissue samples were extracted from the dorsolateral prefrontal cortex of 153 deceased individuals (Mage = 35.42; 62 % male; 77 % European ancestry). The study included 72 opioid samples, 53 psychiatric controls, and 28 normal controls. The epigenome-wide analysis was implemented using the Illumina MethylationEPIC BeadChip; analyses adjusted for sociodemographic characteristics, negative control principal components, ancestry principal components, cellular composition, and surrogate variables. Horvath's epigenetic age and Levine's PhenoAge were calculated, and gene set enrichment analyses were performed.ResultsAlthough no CpG sites survived false-discovery rate correction for multiple testing, 13 sites surpassed a relaxed significance threshold (p < 1.0 × 10-5). One of these sites was located within Netrin-1, a gene implicated in kappa opioid receptor activity. There was an association between opioid use and accelerated PhenoAge (b = 2.24, se = 1.11, p = .045). Gene set enrichment analyses revealed enrichment of differential methylation in GO and KEGG pathways broadly related to substance use.ConclusionsNetrin-1 may be associated with opioid overdose, and future research with larger samples across stages of opioid use will elucidate the complex genomics of opioid abuse.
| S-EPMC8026744 | biostudies-literature
Project description:To identify possible target molecules for acute alcohol intoxication therapy, we used microarray analysis to compare cerebella gene expression profiles of control and acute alcohol-intoxicated rats. We first established a model of acute alcohol intoxication in SD rats, and then used rat cDNA microarray to profile mRNA expression in the cerebella of alcohol-intoxicated rats (experimental group) and saline-treated rats (control group).
2013-07-29 | GSE49303 | GEO
Project description:To identify possible target molecules for acute alcohol intoxication therapy, we used microarray analysis to compare cerebella gene expression profiles of control and acute alcohol-intoxicated rats. We first established a model of acute alcohol intoxication in SD rats, and then used rat cDNA microarray to profile mRNA expression in the cerebella of alcohol-intoxicated rats (experimental group) and saline-treated rats (control group). A six chip study using total RNA recovered from three separate experimental groups and three separate control groups. We first established a model of acute alcohol intoxication in SD rats, and then used rat cDNA microarray to profile mRNA expression in the cerebella of alcohol-intoxicated rats (experimental group) and saline-treated rats (control group). Cerebellar tissues from three rats were ground to a mixed sample,so we use 3 rats in one group.
2013-07-29 | E-GEOD-49303 | biostudies-arrayexpress
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:Cholera toxin (CT) is the etiological agent of cholera. Here we report that multiple classes of fucosylated glycoconjugates function in CT binding and intoxication of intestinal epithelial cells. In Colo205 cells, knockout of B3GNT5, the enzyme required for synthesis of lacto- and neolacto-series glycosphingolipids (GSLs), reduces CT binding but sensitizes cells to intoxication. Overexpressing B3GNT5 to generate more fucosylated GSLs confers protection against intoxication, indicating that fucosylated GSLs act as decoy receptors for CT. Knockout (KO) of B3GALT5 causes increased production of fucosylated O-linked and N-linked glycoproteins, and leads to increased CT binding and intoxication. Knockout of B3GNT5 in B3GALT5 KO cells eliminates production of fucosylated GSLs but increases intoxication, identifying fucosylated glycoproteins as functional receptors for CT. These findings provide insight into molecular determinants regulating CT sensitivity of host cells.
2024-08-31 | GSE242156 | GEO
Project description:Modulation of the mouse liver epigenome following TCPOBOP exposure
| PRJNA408126 | ENA
Project description:To uncover the role of opioid induced dysbiosis in disrupting intestinal homeostasis, we conducted a multi-omics analysis with gut microbial, metabolite and intestinal transcriptomics data
2023-08-30 | GSE230095 | GEO
Project description:The Opioid Use Disorder epidemic led to an increase in cases of Nenonatal Opioid Withdrawal Syndrome (NOWS) in infants born to opioid-dependent mothers. Hallmark features include weight loss, irritability, inconsolability, insomnia, and increased pain sensitivity. The neurobiological basis of NOWS is largely unknown. Improved mouse models will facilitate mechanistic and treatment discovery. We treated neonatal outbred Cartworth Farms White (CFW) mice (Swiss Webster) with morphine sulfate (15 mg/kg, s.c.) twice daily on postnatal day (P)1 through P14, the approximate third trimester-equivalent of human gestation. Weight loss was monitored and behavioral symptoms were measured on P7 and P14 at 16 h post-morphine. Brainstem containing pons and medulla was collected on P14 and processed for transcriptome analysis via mRNA sequencing (RNA-seq). Morphine induced weight loss from P2 to P14 that remained at P21 and P50. Repeated morphine also induced a delayed self-righting latency at P4 and a persistent, female-specific delay at P14. Morphine-treated females also showed an earlier increase in ultrasonic vocalizations (USVs) on P7. Both morphine-treated sexes showed a large increase in USVs on P14. Furthermore, thermal nociception via hot plate and tail withdrawal assays indicated that mice exhibited thermal hyperalgesia on P7 and P14, with females showing greater hyperalgesia (tail withdrawal) on P7. Morphine-treated mice also exhibited anxiety-like behavior at P21 (open field). Finally, brainstem transcriptome analysis identified a canonical gene set relevant to opioid signaling in males and a distinct gene set in females that was enriched for ribosomal proteins, mitochondrial function and neurodegenerative disorders. Sex-specific transcriptomic neuroadaptations implicate sex-specific treatments.
2019-11-27 | GSE141066 | GEO
Project description:The opioid epidemic represents a national crisis. Oxycodone is one of the most prescribed opioid medications in the United States, whereas buprenorphine is currently the most prescribed medication for opioid use disorder (OUD) pharmacotherapy. Given the extensive use of prescription opioids and the global opioid epidemic, it is essential to understand how opioids modulate brain cell type function at the single-cell level. We performed single nucleus RNA-seq (snRNA-seq) using iPSC-derived forebrain organoids from three male OUD subjects in response to oxycodone, buprenorphine, or vehicle for seven days. We utilized the snRNA-seq data to identify differentially expressed genes following drug treatment using the Seurat integrative analysis pipeline. We utilized iPSC-derived forebrain organoids and single-cell sequencing technology as an unbiased tool to study cell-type-specific and drug-specific transcriptional responses. After quality control filtering, we analyzed 25787 cells and identified sixteen clusters using unsupervised clustering analysis. Our results reveal distinct transcriptional responses to oxycodone and buprenorphine by iPSC-derived brain organoids from patients with OUD. Specifically, buprenorphine displayed a significant influence on transcription regulation in glial cells. However, oxycodone induced type I interferon signaling in many cell types, including neural cells in brain organoids. Finally, we demonstrate that oxycodone, but not buprenorphine activated STAT1 and induced the type I interferon signaling in patients with OUD. These data suggest that elevation of STAT1 expression associated with OUD might play a role in transcriptional regulation in response to oxycodone. In summary, our results provide novel mechanistic insight into drug action at single-cell resolution.
2024-07-18 | GSE210206 | GEO