Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Chronic opioid treatment arrests neurodevelopment and alters synaptic activity in human midbrain organoids

ABSTRACT: Understanding the impact of long-term opioid exposure on the embryonic brain is critical due to the surging number of pregnant mothers with opioid dependency, but has been limited by human brain inaccessibility and cross-species differences in animal models. Here we establish a human midbrain model that uses hiPSC-derived midbrain organoids and apply it to assess cell-type-specific responses to acute and chronic fentanyl treatment and fentanyl withdrawal. Single-cell mRNA sequencing of 25,510 cells from organoids in different treatment groups indicated that chronic fentanyl treatment arrests neuronal subtype specification during early midbrain development and alters synaptic activity and neuron projection. In contrast, acute fentanyl treatment increases dopamine release but does not significantly alter gene expression related to cell lineage development. These results provide the first examination of the effects of opioid exposure on human midbrain development at the single cell level.

ORGANISM(S): Homo sapiens

PROVIDER: GSE260711 | GEO | 2024/03/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

microRNA expression and opioid signaling

Project description:To study the relationship between microRNAs and Î¼-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

microRNA expression and opioid signaling

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

Opioid withdrawal produces sex-specific effects on fentanyl-vs.-food choice and mesolimbic transcription

Project description:Background: Opioid withdrawal is a key driver of opioid addiction and an obstacle to recovery. However, withdrawal effects on opioid reinforcement and mesolimbic neuroadaptation are understudied and the role of sex is largely unknown. Methods: Male (n=13) and female (n=12) rats responded under a fentanyl-vs.-food “choice” procedure during daily 2h sessions. In addition to the daily choice sessions, rats were provided extended access to fentanyl during 12h self-administration sessions. After two weeks of this selfadministration regimen, the nucleus accumbens (NAc) and ventral tegmental area (VTA) of a subset of rats were subjected to RNA sequencing. In the remaining rats, a third week of this self-administration regimen was conducted, during which methadone effects on fentanyl-vs.-food choice were determined. Results: Prior to opioid dependence, male and female rats similarly allocated responding between fentanyl and food. Abstinence from extended fentanyl access elicited similar increases in somatic withdrawal signs in both sexes. Despite similar withdrawal signs and extended access fentanyl intake, opioid withdrawal was accompanied by a maladaptive increase in fentanyl choice in males, but not females. Behavioral sex differences corresponded with a greater number of differentially expressed genes in the NAc and VTA of opioidwithdrawn females relative to males. Methadone blocked withdrawal-associated increases in fentanyl choice in males, but failed to further decrease fentanyl choice in females. Conclusions: These results provide foundational evidence of sex-specific neuroadaptations to opioid withdrawal, which may be relevant to the female-specific resilience to withdrawal-associated increases in opioid choice and aid in the identification of novel therapeutic targets.

2021-05-06 | GSE173959 | GEO

The synthetic opioid fentanyl increases HIV replication and chemokine co-receptor expression in lymphocyte cell lines

Project description:The illicit use of synthetic opioids such as fentanyl has led to a serious public health crisis in the United States. People with opioid use disorder are more likely to contract infections such as HIV and viral hepatitis. While several drugs of abuse are known to enhance viral replication and to suppress immunologic responses, the effects of synthetic opioids on HIV pathogenesis have not been investigated thoroughly. Thus, we examined the impact of fentanyl on HIV-susceptible and HIV-infected cell types and chemokine receptor expression in vitro. TZM-bl and HIV-infected lymphocyte cells were incubated with fentanyl at concentrations of 1 ng, 100 ng, and 10 ug. Expression levels of the CXCR4 and CCR5 chemokine receptors were measured in cell lysates, and HIV p24 antigen was quantified in culture supernatants by ELISA. HIV proviral DNA was quantified in cells using SYBR RT-PCR targeting the pol gene. Cell viability in the presence of drug was detected by the MTT Cell Proliferation Assay. RNA-seq and miRNAseq was performed to characterize cellular gene regulation in the presence of fentanyl. Fentanyl enhanced expression of CXCR4 and CCR5 protein levels in a dose-dependent manner in HIV-susceptible and HIV-infected cells. Similarly, fentanyl induced viral expression in HIV-exposed TZM-bl cells and in multiple HIV-infected lymphocyte cell lines. Multiple genes associated with apoptosis, antiviral / interferon response, chemokine signaling, and NFκB signaling were differentially regulated by fentanyl. These data demonstrate that the synthetic opioid fentanyl impacts HIV replication and chemokine co-receptor expression in HIV-susceptible and HIV-infected cells. Increased virus levels also suggest that opioid use may increase the likelihood of transmission to others and accelerate disease progression.

2022-10-19 | GSE216044 | GEO

The synthetic opioid fentanyl increases HIV replication and chemokine co-receptor expression in lymphocyte cell lines

Project description:Fentanyl enhanced expression of CXCR4 and CCR5 protein levels and viral expression in a dose-dependent manner in multiple HIV-susceptible and HIV-infected cell lines. Multiple genes associated with apoptosis, antiviral / interferon response, chemokine. signaling, and NFκB signaling were differentially regulated by fentanyl. Thus fentanyl impacts HIV replication and chemokine co-receptor expression in HIV-susceptible and HIV-infected lymphocyte cell lines suggesting that opioid use may increase the likelihood of transmission to others and accelerate disease progression.

2022-10-20 | GSE216124 | GEO

The synthetic opioid fentanyl increases HIV replication expression in macrophages

Project description:The illicit use of synthetic opioids such as fentanyl has led to a serious public health crisis in the US. People with opioid use disorder are more likely to contract infections such as HIV and viral hepatitis and experience more severe disease. While several drugs of abuse are known to enhance viral replication and to suppress immunologic responses, the effects of synthetic opioids on HIV pathogenesis have not been investigated thoroughly. Thus, we examined the impact of fentanyl on macrophage cell line U937 and monocyte derived macrophage cells and chemokine receptor expression in vitro.

2024-08-28 | GSE241769 | GEO

Comparison of RNA responses to fentanyl in two mouse strains

Project description:An increase in opioid-overdose deaths was evident before the COVID-19 pandemic, and has escalated since its onset. Fentanyl, a highly potent synthetic opioid, is the primary driver of these recent trends. The current study used two inbred mouse strains, C57BL/6 J and A/J, to investigate the genetics of behavioral responses to fentanyl. Mice were tested for conditioned place preference and fentanyl-induced locomotor activity. C57BL/6J mice formed a conditioned place preference to fentanyl injections and fentanyl increased their activity. Neither effect was noted in A/J mice. We conducted RNA-sequencing on the nucleus accumbens of mice used for fentanyl-induced locomotor activity. Surprisingly, we noted few differentially expressed genes using treatment as the main factor. However many genes differed between strains. We validated differences in two genes: suppressor APC domain containing 1 (Sapcd1) and Glyoxalase 1 (Glo1), with quantitative PCR on RNA from the nucleus accumbens and prefrontal cortex. In both regions A/J mice had significantly higher expression of both genes than did C57BL/6 J. In prefrontal cortex, fentanyl treatment decreased Glo1 mRNA. Glyoxalase 1 catalyzes the detoxification of reactive alpha-oxoaldehydes such as glyoxal and methylglyoxal, is associated with anxiety and activity levels, and its inhibition reduces alcohol intake. We suggest that future studies assess the ability of Glo1 and related metabolites to modify opioid intake.

2023-01-10 | GSE222569 | GEO

Changes in gut microbiome composition drive fentanyl intake and striatal proteomic changes

Project description:Opioid use disorder (OUD) is a public health crisis currently being exacerbated by increases in use of fentanyl; therefore, the identification of novel biomarkers and treatment strategies is critical. Here, we define how manipulations of the gut microbiome drive fentanyl intake, fentanyl seeking, and alter proteomic plasticity in the nucleus accumbens. These findings establish clear relevance for gut-brain signaling in OUD, and lay foundations for further translational work in this space.

2024-05-22 | PXD035810 | Pride

Single Nucleus Transcriptomes from the Ventral Midbrain of Opioid Overdose Cases and Controls

Project description:Dynamic interactions of neurons and glia in the ventral midbrain (VM) mediate reward and addiction behavior. We studied gene expression in 212,713 VM single nuclei from 95 human opioid overdose cases and drug-free controls. Chronic exposure to opioids left numerical proportions of VM glial and neuronal subtypes unaltered, while broadly affecting glial transcriptomes, involving 9.5 - 6.2% of expressed genes within microglia, oligodendrocytes, and astrocytes, with prominent activation of the immune response including interferon, NFkB signaling, and cell motility pathways, sharply contrasting with down-regulated expression of synaptic signaling and plasticity genes in VM non-dopaminergic neurons. VM transcriptomic reprogramming in the context of opioid exposure and overdose included 325 genes with genetic variation linked to substance use traits in the broader population, thereby pointing to heritable risk architectures in the genomic organization of the brain’s reward circuitry.

2023-08-18 | GSE240457 | GEO

Vitamin D deficiency exacerbates UV/endorphin and opioid addiction

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

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data