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Dose-dependent consequences of sub-chronic fentanyl exposure on neuron and glial co-cultures

ABSTRACT: Dose-dependent consequences of sub-chronic fentanyl exposure on neuron and glial co-cultures

PROVIDER: PRJNA856310 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR20005966.fastq.gz	Fastqsanger.gz
	SRR20005967.fastq.gz	Fastqsanger.gz
	SRR20005968.fastq.gz	Fastqsanger.gz
	SRR20005969.fastq.gz	Fastqsanger.gz
	SRR20005970.fastq.gz	Fastqsanger.gz

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Dose-dependent consequences of sub-chronic fentanyl exposure on neuron and glial co-cultures

Project description:It remains poorly understood what and how changes in brain activity from chronic fentanyl use influences the respective behavioral outcome. We examined the functional and molecular changes to cortical neural network activity following sub-chronic exposure to two fentanyl concentrations, a low (0.01 µM) and high (10 µM) dose from primary rat co-cultures, containing cortical neurons, astrocytes, and oligodendrocyte-lineage cell.

2022-08-31 | GSE207606 | GEO

Dose-dependent consequences of sub-chronic fentanyl exposure on neuron and glial co-cultures.

Project description:Fentanyl is one of the most common opioid analgesics administered to patients undergoing surgery or for chronic pain management. While the side effects of chronic fentanyl abuse are recognized (e.g., addiction, tolerance, impairment of cognitive functions, and inhibit nociception, arousal, and respiration), it remains poorly understood what and how changes in brain activity from chronic fentanyl use influences the respective behavioral outcome. Here, we examined the functional and molecular changes to cortical neural network activity following sub-chronic exposure to two fentanyl concentrations, a low (0.01 μM) and high (10 μM) dose. Primary rat co-cultures, containing cortical neurons, astrocytes, and oligodendrocyte precursor cells, were seeded in wells on either a 6-well multi-electrode array (MEA, for electrophysiology) or a 96-well tissue culture plate (for serial endpoint bulk RNA sequencing analysis). Once networks matured (at 28 days in vitro), co-cultures were treated with 0.01 or 10 μM of fentanyl for 4 days and monitored daily. Only high dose exposure to fentanyl resulted in a decline in features of spiking and bursting activity as early as 30 min post-exposure and sustained for 4 days in cultures. Transcriptomic analysis of the complex cultures after 4 days of fentanyl exposure revealed that both the low and high dose induced gene expression changes involved in synaptic transmission, inflammation, and organization of the extracellular matrix. Collectively, the findings of this in vitro study suggest that while neuroadaptive changes to neural network activity at a systems level was detected only at the high dose of fentanyl, transcriptomic changes were also detected at the low dose conditions, suggesting that fentanyl rapidly elicits changes in plasticity.

| S-EPMC9403314 | biostudies-literature

Adaptations in nucleus accumbens neuron subtypes mediate negative affective behaviors in fentanyl abstinence

Project description:We used RNAseq to evaluate changes in nucleus accumbens (NAc) D1 and D2 translatomes from fentanyl abstinent mice.

2022-07-31 | GSE209969 | GEO

1,25-dihydroxyvitamin D3-induced genes in mouse mixed neuron-glial cell cultures

Project description:Transcriptomic response of mouse mixed neuron-glial cell cultures to 1,25-dihydroxyvitamin D3 6 samples are analysed with three biological replicates in two conditions, control versus 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)

2013-03-25 | E-GEOD-41184 | biostudies-arrayexpress

1,25-dihydroxyvitamin D3-induced genes in mouse mixed neuron-glial cell cultures

Project description:Transcriptomic response of mouse mixed neuron-glial cell cultures to 1,25-dihydroxyvitamin D3

2013-03-25 | GSE41184 | 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

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 elicited transcriptomic alterations related to viral replication, immune response, and inflammation in vitro.

Project description:The US is in the midst of a major drug epidemic fueled in large part by the widespread recreational use of syntheticopioids such as fentanyl. we evaluated the impact of fentanyl using in cell lines that replicate infectious viruses. RNAseq identified a number of hepatocyte genes that were differentially regulated by fentanyl, including those related to apoptosis, the antiviral / interferon response, chemokine signaling, and NFkB signaling.

2021-04-21 | GSE167922 | 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

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