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Transcriptional response of rat cerebrocortical tissue following acute exposure to permethrin or deltamethrin.

ABSTRACT: Pyrethroids are neurotoxicants that disrupt nervous system function by interacting with a variety of membrane bound ion channels on neuronal plasma membranes. This study is designed to investigate the transcriptional events downstream of pyrethroid-induced disruption of nervous system excitability. Adult, male Long-Evans rats were orally dosed in vivo with a single dose of either permethrin (1, 10, or 100 mg/kg) or deltamethrin (0.3, 1, 3 mg/kg) at levels that produce only modest behaviroal effects in the whole animal (Wolansky et al. 2006). Transcriptional profiles were obtained from frontal cerebrocortical tissue 6 hours after acute exposure. The primary goals were 1) to identify dose-responsive biomarkers of effect for pyrethroids and 2) identify sensitive intracellular signaling or metabolic pathways sensitive to pyrethroid compounds. Keywords: dose response

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE7955 | GEO | 2007/10/15

SECONDARY ACCESSION(S): PRJNA100699

REPOSITORIES: GEO

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Transcription profiling of rat cerebrocortical tissue following acute exposure to permethrin or deltamethrin.

Project description:Pyrethroids are neurotoxicants that disrupt nervous system function by interacting with a variety of membrane bound ion channels on neuronal plasma membranes. This study is designed to investigate the transcriptional events downstream of pyrethroid-induced disruption of nervous system excitability. Adult, male Long-Evans rats were orally dosed in vivo with a single dose of either permethrin (1, 10, or 100 mg/kg) or deltamethrin (0.3, 1, 3 mg/kg) at levels that produce only modest behaviroal effects in the whole animal (Wolansky et al. 2006). Transcriptional profiles were obtained from frontal cerebrocortical tissue 6 hours after acute exposure. The primary goals were 1) to identify dose-responsive biomarkers of effect for pyrethroids and 2) identify sensitive intracellular signaling or metabolic pathways sensitive to pyrethroid compounds. Experiment Overall Design: In total 60 samples were analyzed in the present study: vehicle control (n = 12), 1 mg/kg permethrin (n=8), 10 mg/kg permethrin (n = 8), 100 mg/kg permethrin (n = 8), 0.3 mg/kg deltamethrin (n = 8), 1 mg/kg deltamethrin (n = 8), 3 mg/kg deltamethrin (n = 8). Transcriptional profiles for each test subject were obtained independently, without sample pooling. Experiment Overall Design: The publication will include an Appendix Table comparing the variability of RMA values (see Sample VALUE columns) to that of GCOS values (see Sample .CHP files).

2008-06-17 | E-GEOD-7955 | biostudies-arrayexpress

Effects of a pyrethroid pesticide deltamethrin on gene expression profiles in mouse neuroblastoma Neuro2a cell

Project description:Pyrethroids are one of the most commonly used classes of synthetic pesticides detected from all individuals in every part of the world; however, the mechanisms underlying the neurotoxicity of pyrethroids were still remain unclear. To understand neurotoxic mechanisms of DM, we investigated transcriptome changes by exposure to a pyrethroid pesticide deltamethrin (DM) in the mouse neuroblastoma Neuro2a cell.

2021-06-03 | GSE176000 | GEO

Developmental pyrethroid exposure disrupts molecular pathways for circadian rhythms and synaptic plasticity in mouse brain.

Project description:Neurodevelopmental disorders (NDD) are a category of pervasive disorders of the developing nervous system with few or no recognized biomarkers. A significant portion of the risk for NDD, including ADHD, is contributed by the environment, and exposure to pyrethroid pesticides during pregnancy has been identified as a potential risk factor for NDD in the unborn child. We recently showed that low-dose developmental exposure to the pyrethroid pesticide deltamethrin (DPE) in mice causes male-biased changes to ADHD- and NDD-relevant behaviors as well as the striatal dopamine system. Here, we used a multiomics approach to determine the broadest possible set of pharmacologically relevant changes in mouse brain resulting from DPE. Using a litter-based, split-sample design, we deltamethrin mouse dams during pregnancy and lactation to deltamethrin (3 mg/kg or vehicle every 3 days) at a concentration well below the EPA-determined benchmark dose used for regulatory guidance. The male offspring were raised to adulthood, euthanized, and whole brain samples pulverized and divided for split-sample transcriptomics, kinomics and multiomics integration. The transcriptome revealed alterations to multiple canonical clock genes. The kinome revealed changes in the activity of multiple kinases involved in synaptic plasticity, and broadly in the AGC kinase family. Multiomics integration revealed a dysregulated protein-protein interaction network containing primary clusters for MAP kinase cascade, synaptic function, and regulation of apoptosis. These results demonstrate that DPE causes a multi-modal biophenotype in the brain relevant to ADHD and identifies new potential avenues for therapeutics.

2023-08-28 | GSE241185 | GEO

Molecular bases of P450-mediated resistance to the neonicotinoid insecticide imidacloprid in the mosquito Ae. aegypti

Project description:Resistance to chemical insecticides including pyrethroids, the main insecticide class used against mosquitoes, led to a regain of interest for neonicotinoids. In this context, the present study aims at characterizing the molecular basis of neonicotinoid resistance in the mosquito Aedes aegypti. Resistance mechanisms were studied by combining transcriptomic and genomic data obtained from a laboratory strain selected at the larval stage for 30 generations with imidacloprid (Imida-R line). After thirty generations of selection, larvae of Imida-R line showed a 8-fold increased resistance to imidacloprid and a significant cross-tolerance to the pyrethroids permethrin and deltamethrin. Cross-resistance to pyrethroids was only observed in adults when larvae were previously exposed to imidacloprid suggesting a low but inducible expression of resistance alleles at the adult stage. Resistance of the Imida-R line was associated with a slower larval development time in females. Multiple detoxification enzymes were over-transcribed in larvae in association with resistance including the P450s CYP6BB2, CYP9M9 and CYP6M11 previously associated with pyrethroid resistance. Some of them together with their redox partner NADPH P450 reductase were also affected by non-synonymous mutations associated with resistance. Combining genomic and transcriptomic data allowed identifying promoter variations associated with the up-regulation of CYP6BB2 in the resistant line. Overall, these data confirm the key role of P450s in neonicotinoid resistance in Ae. aegypti and their potential to confer cross-resistance to pyrethroids, raising concerns about the use of neonicotinoids for resistance management in this mosquito species.

2021-05-07 | GSE174009 | GEO

Multigene biomarkers of pyrethroid exposure: preliminary experiments: 60k microarrays

Project description:We describe initial development of RNA profiling-based assays for detecting pyrethroid pesticides in water. We conducted 48-hour flow-through exposures of Pimephales promelas larvae to lab water and eight nominal concentrations of each of four pyrethroid insecticides: bifenthrin, cypermethrin, esfenvalerate, and (trans) permethrin. Concentration-response curves suggest steep dose responses, and LC50s below most published values. Expression microarray analysis of whole larvae suggests transcriptomic changes can be used to detect these pyrethroids at concentrations well below P. promelas LC50s, and below LC50s of about 70% of aquatic metazoan species. Geneset analysis and intersections between lists of differentially expressed genes failed to identify substantial functional overlaps between these toxicants. Geneset analysis was sensitive to parameter choice, which may reflect the large number of genes analyzed relative to the number of samples, and substantial biological variability relative to effect sizes. Several identified GO terms can be rationalized based on known pyrethroid action, but implications of other highlighted GO terms are unclear.

2018-10-31 | GSE113285 | GEO

Comparison between opioid (morphine) and vehicle treatments in mouse trigeminal ganglia and nucleus accumbens

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

Deltamethrin exposure time course performed on highly resistant Anopheles coluzzii

Project description:Ascertain the transcriptional response of the major malaria vector Anopheles coluzzii to the pyrethroid deltamethrin over ten time points.

2021-01-01 | E-MTAB-9422 | biostudies-arrayexpress

MeHg-induced encephalopathy

Project description:In this dose series pregnant CD-1 (outbred) dams were exposed to methylmercury (MeHg) as monomethylmercuric chloride injected intraperitoneally on 9 d.p.c. Test doses were 10.0 mg/kg and below. This regimen induces symptoms of Fetal Minimata Disease (FMD) in term fetuses. Risks with respect to FMD for the various test doses were 10.0 mg/kg (40% risk), 5.0 mg/kg (20% risk), 2.5 mg/kg (NOAEL), and 1.25 mg/kg (subNOAEL). All measurements were on RNA from the embryonic forebrain (prosencephalon and surrounding tissue) at 3.0h post-treatment. Keywords = dose series Keywords = mercury Keywords = embryo Keywords = Fetal Minamata Disease Keywords: dose response

2004-03-11 | GSE1075 | GEO

Transcriptomic profiling of S2/S3 proximal tubules in response to LPS treatment

Project description:To investigate the mechanisms of endotoxin-mediated kidney injury as well as renoprotective effects of endotoxin preconditioning, we performed manual microdissection of S2/S3 proximal tubules in mice as follows: 1) Non-preconditioned mice subjected to single-dose 5 mg/kg LPS (0111:B4) i.p. for 4 hrs. 2) Non-preconditioned mice subjected to single-dose 5 mg/kg LPS (0111:B4) for 24 hrs. 3) Preconditioned mice subjected to 0.25 mg/kg LPS followed 24 hour later by 5 mg/kg LPS for 4 hrs. 4) Preconditioned mice subjected to 0.25 mg/kg LPS followed 24 hour later by 5 mg/kg LPS for 24 hrs. 5) Control mice (untreated).

2018-10-06 | GSE120879 | GEO

Multigene biomarkers of pyrethroid exposure: preliminary experiments: 15k microarrays

Project description:We describe initial development of RNA profiling-based assays for detecting pyrethroid pesticides in water. We conducted 48-hour flow-through exposures of Pimephales promelas adults and larvae to lab water and eight nominal concentrations of each of four pyrethroid insecticides: bifenthrin, cypermethrin, esfenvalerate, and (trans) permethrin. Concentration-response curves suggest steep dose responses, and LC50s below most published values. Expression microarray analysis of dissected brains from adults and whole larvae exposed to cypermethrin and bifenthrin suggests both assay formats can be used to detect these pyrethroids at concentrations well below P. promelas LC50s, and below LC50s of about 70% of aquatic metazoan species. Geneset analysis and intersections between lists of differentially expressed genes failed to identify substantial functional overlaps between these toxicants. Geneset analysis was sensitive to parameter choice, which may reflect the large number of genes analyzed relative to the number of samples, and substantial biological variability relative to effect sizes. Several identified GO terms can be rationalized based on known pyrethroid action, but implications of other highlighted GO terms are unclear.

2018-10-31 | GSE113284 | GEO

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