Developmental opioid exposure results in lasting transcriptome alterations in zebrafish (Danio rerio) embryos
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1237347 | ENA |
REPOSITORIES: ENA
Dataset's files
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| SRR32737834_1.fastq.gz | Fastqsanger.gz | |||
| SRR32737834_2.fastq.gz | Fastqsanger.gz | |||
| SRR32737836_1.fastq.gz | Fastqsanger.gz | |||
| SRR32737836_2.fastq.gz | Fastqsanger.gz |
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Project description:The opioid epidemic has introduced significant public health challenges with little knowledge regarding the consequences of opioid exposure during embryonic development. While neurobehavioral effects of developmental opioid exposure are well-documented, early effects of exposure remain largely unexplored. We investigated the effects of oxycodone and fentanyl exposure on gene expression in zebrafish (Danio rerio) embryos using whole embryo RNA sequencing. Embryos were exposed to environmentally relevant (Oxycodone HCl 10.6pg/mL and Fentanyl Citrate 0.629pg/mL) and therapeutically relevant (Oxycodone HCl 35.14ng/mL and Fentanyl Citrate 3.14ng/mL) from 2 to 24 hours post-fertilization (hpf), followed by another 24hrs of opioid-free development. RNA sequencing at 48hpf revealed dose and drug specific gene expression changes. Lower doses of oxycodone and fentanyl both induced more differentially expressed genes (DEGs) than higher doses, potentially indicative of opioid receptor desensitization occurring at higher concentrations. In total, 892 DEGs were identified across all conditions indicating continued differential gene expression well after cessation of opioid exposure. Gene ontology analysis revealed changes in gene expression relating to extracellular matrix (ECM) organization, cell adhesion, and visual and nervous system formation. Key pathways include axon guidance, synapse formation, and ECM biosynthesis/remodeling all of which have potential implications on neural connectivity and sensory development. These findings demonstrate that developmental exposure to opioids induced persistent transcriptomic changes which may have lasting implications for structural integrity and function in vertebrate nervous systems, providing insights into the molecular mechanisms of opioid-induced alterations during development.
2025-06-04 | GSE292183 | GEO
Project description:Opioid use during pregnancy is a growing public health concern, with in utero exposure to synthetic opioids like fentanyl linked to Neonatal Opioid Withdrawal Syndrome (NOWS) and long-term neurobehavioral impairments. However, the long-term neurodevelopmental consequences of in utero opioid exposure remain poorly understood. We developed a translationally relevant rat model of perinatal fentanyl exposure to investigate the behavioral and molecular outcomes of prenatal opioid exposure. Offspring born to fentanyl-exposed dams showed reduced survival rates, lower body weight, and spontaneous withdrawal symptoms. In adolescence, they displayed mechanical hypersensitivity and behaviors consistent with negative affect. In adulthood, these rats exhibited enhanced fentanyl self-administration, increased reinstatement behavior, and elevated plasma corticosterone levels during withdrawal. Furthermore, they showed increased risk-taking behavior in the Elevated Plus Maze, suggesting altered anxiety or impulsivity regulation. To investigate molecular correlates of these phenotypes, we performed transcriptomic profiling of the central amygdala of adult rats. Differential gene expression and gene set enrichment analyses revealed that perinatal fentanyl exposure led to dysregulation of pathways involved in synaptic signaling, neurodevelopment, GPCR signaling, and immune responses. These transcriptional changes provide a molecular framework for understanding how early fentanyl exposure leads to long-lasting vulnerability to stress and addiction-related behaviors. These findings underscore the lasting impact of perinatal opioid exposure on brain function and behavior and support the utility of this model for translational research on NOWS and opioid-related neuropsychiatric risk.
2025-06-27 | GSE296650 | GEO
Project description:Background: Opioid use disorder (OUD) has emerged as a severe, ongoing public health emergency. Current treatments for OUD are unsuccessful in lead to lasting abstinence in most users. This underscores the lasting effects of chronic opioid use and emphasizes the need to understand the molecular mechanisms of drug seeking and taking, but also how those alterations persist through acute and protracted withdrawal. Methods: Here, we used RNA sequencing in post-mortem human tissue from males (n=10) and females (n=10) with OUD and age and sex-matched control subjects. We compared molecular alterations associated with human OUD in the nucleus accumbens (NAc) to mouse and rat models of non-volitional (n=3-6 per group per sex) and volitional (n=5-6 per group per sex) exposure to opioids across distinct stages of opioid use and withdrawal (acute and prolonged). Results: We found that the molecular signature in the NAc of females with OUD mirrored effects seen in the NAc of female rodents in a non-volitional paradigm at all stages of exposure. Conversely, males with OUD showed a similar expression profile to rodents with volitional exposure, but only during the acute withdrawal phase. Shared co-expression networks were involved in post-transcriptional modification of RNA and epigenetic modification of chromatin state. Conclusions: Our results provide fundamental insight into the conserved molecular pathways altered by opioids across species, with evidence suggesting that alterations in females with OUD may be driven by drug exposure, while alterations in males with OUD may be driven by volitional intake.
2025-02-21 | GSE289002 | GEO
Project description:Alcohol use disorder is marked by disrupted behavioral and emotional states which can persist into abstinence. The enduring synaptic alterations that remain despite the absence of alcohol are of interest for interventions to prevent relapse. 28 male rhesus macaques underwent over 20 months of alcohol drinking interspersed with three 30-day forced abstinence periods. After the last abstinence period, we paired ex vivo voltammetry in nucleus accumbens slices with RNA-sequencing of the ventral tegmental area. We found persistent augmentation of dopamine transporter function, kappa opioid receptor sensitivity, and dynorphin release – all inhibitory regulators which act to decrease extracellular dopamine. Surprisingly, though transcript expression was not altered, the relationship between gene expression and functional readouts of these encoded proteins was highly dynamic and altered by drinking history. Therefore, the long-lasting synaptic impact of alcohol use suggests that assessment of transcript-function relationships may provide avenues for precision therapeutics targeted to specific synaptic pathophysiologies.
2024-04-16 | GSE244557 | 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:Due to the current opioid epidemic, a better understanding of genetic and environmental factors that contribute to opioid addiction is warranted. To explore the potential causative role of VitD in opioid addiction , we used multiple pharmacologic approaches and genetic mouse models. We used profiled the transcriptome of key brain reward regions upon morphine treatment in vitamin D receptor KO and wild type mice. Our results highlight the role of VitD deficiency in the development of addiction and suggest a potential therapeutic benefit of VitD supplementation for VitD deficient individuals in the prevention and management of addiction.
2021-04-25 | GSE171683 | GEO
Project description:Bekaert2012 - Reconstruction of D.rerio Metabolic Network
Danio rerio
metabolic model accounting for subcellular compartmentalisation (ZebraGEM)
This SBML representation of the D. rerio
(zebrafish) metabolic network is made available under the Creative Commons Attribution-Share Alike 3.0 Unported Licence (see www.creativecommons.org
).
This model is described in the article:
Reconstruction of Danio rerio Metabolic Model Accounting for Subcellular Compartmentalisation.
Bekaert M.
PLoS One. 2012;7(11):e49903.
Abstract:
Plant and microbial metabolic engineering is commonly used in the production of functional foods and quality trait improvement. Computational model-based approaches have been used in this important endeavour. However, to date, fish metabolic models have only been scarcely and partially developed, in marked contrast to their prominent success in metabolic engineering. In this study we present the reconstruction of fully compartmentalised models of the Danio rerio (zebrafish) on a global scale. This reconstruction involves extraction of known biochemical reactions in D. rerio for both primary and secondary metabolism and the implementation of methods for determining subcellular localisation and assignment of enzymes. The reconstructed model (ZebraGEM) is amenable for constraint-based modelling analysis, and accounts for 4,988 genes coding for 2,406 gene-associated reactions and only 418 non-gene-associated reactions. A set of computational validations (i.e., simulations of known metabolic functionalities and experimental data) strongly testifies to the predictive ability of the model. Overall, the reconstructed model is expected to lay down the foundations for computational-based rational design of fish metabolic engineering in aquaculture.
This model is hosted on BioModels Database
and identified by: MODEL1204120000
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. PMID: 20587024
.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to [CC0 Public Domain Dedication>http://creativecommons.org/publicdomain/zero/1.0/] for more information.
2005-01-01 | MODEL1204120000 | BioModels
Project description:Opioid use during pregnancy can lead to negative infant health outcomes, including neonatal opioid withdrawal syndrome (NOWS). NOWS comprises gastrointestinal, autonomic nervous system, and neurological dysfunction that manifest during spontaneous withdrawal. Current treatments involve non-pharmacological and pharmacological interventions, however, there is no one standardized approach, in part because of variability in NOWS severity. To effectively model NOWS traits in mice, we used a third trimester-approximate opioid exposure paradigm, where neonatal inbred FVB/NJ and outbred Carworth Farms White (CFW) pups were injected twice-daily with morphine (10-15 mg/kg, s.c.) or saline (0.9%, 20 ul/g, s.c.) from postnatal day (P) one to P14. We observed reduced body weight gain, hypothermia, thermal hyperalgesia, and increased ultrasonic vocalizations (USVs). Neonatal USVs are emitted exclusively in isolation to communicate distress and thus serve as a model behavior for affective states. On P14, we observed altered USV syllable profiles during spontaneous morphine withdrawal, including an increase in Complex 3 syllables in FVB/NJ females (but not males) and in CFW mice of both sexes. Brainstem transcriptomics revealed an upregulation of the kappa opioid receptor (Oprk1), whose activation has previously been shown to contribute to withdrawal-induced dysphoria. Treatment with the kappa opioid receptor (KOR) antagonist, nor-BNI (30 mg/kg, s.c.), significantly reduced USV emission in FVB/NJ females, but not FVB/NJ males during spontaneous morphine withdrawal. Furthermore, treatment with the KOR agonist, U50,488h (0.625 mg/kg, s.c.), was sufficient to increase USV emission on P10 (both sexes) and on P14 (females only) in FVB/NJ mice. Together, these results indicate a female-specific recruitment of the dynorphin/KOR system in neonatal opioid withdrawal symptom severity.
2024-07-09 | GSE271337 | GEO
Project description:Tissues specific transcriptomes of Danio rerio, Danio albolineatus and Danio aesculapii Brain, Liver and Gonads.
2018-11-22 | E-MTAB-7476 | biostudies-arrayexpress
Project description:Investigation of whole genome gene expression level changes in Danio rerio semaphorin6A and plexinA2 morphant animals, compared to the wild-type strain. The morphants analyzed in this study are further described in Ebert AM, Childs SJ, Hehr C, Cechmanek PB, McFarlane S. 2014. Sema6a and Plxna2 mediate spatially regulated repulsion within the developing eye to promote eye vesicle cohesion. Development 141(12):2473-2482.
2017-08-28 | GSE86246 | GEO