Glyphosate infiltrates the brain and increases pro-inflammatory cytokine TNFα: implications for neurodegenerative disorders
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ABSTRACT:
PROVIDER: PRJNA1064995 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27554633_1.fastq.gz | Fastqsanger.gz | |||
| SRR27554633_2.fastq.gz | Fastqsanger.gz | |||
| SRR27554634_1.fastq.gz | Fastqsanger.gz | |||
| SRR27554634_2.fastq.gz | Fastqsanger.gz | |||
| SRR27554635_1.fastq.gz | Fastqsanger.gz |
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Project description:Background: Herbicides are environmental contaminants that have gained much attention due to the potential hazards they pose to human health. Glyphosate, the active ingredient in many commercial herbicides, is the most heavily applied herbicide worldwide. The recent rise in glyphosate application to corn and soy crops correlates positively with increased death rates due to Alzheimer's disease and other neurodegenerative disorders. Glyphosate has been shown to cross the blood-brain barrier in in vitro models, but has yet to be verified in vivo. Additionally, reports have shown that glyphosate exposure increases pro-inflammatory cytokines in blood plasma, particularly TNFα. Methods: Here, we examined whether glyphosate infiltrates the brain and elevates TNFα levels in 4-month-old C57BL/6J mice. Mice received either 125, 250, or 500 mg/kg/day of glyphosate, or a vehicle via oral gavage for 14 days. Urine, plasma, and brain samples were collected on the final day of dosing for analysis via UPLC-MS and ELISAs. Primary cortical neurons were derived from amyloidogenic APP/PS1 pups to evaluate in vitro changes in Aβ40-42 burden and cytotoxicity. RNA sequencing was performed on C57BL/6J brain samples to determine changes in the transcriptome. Results: Our analysis revealed that glyphosate infiltrated the brain in a dose-dependent manner and upregulated TNFα in both plasma and brain tissue post-exposure. Notably, glyphosate measures correlated positively with TNFα levels. Glyphosate exposure in APP/PS1 primary cortical neurons increases levels of soluble Aβ40-42 and cytotoxicity. RNAseq revealed over 200 differentially expressed genes in a dose-dependent manner and cell-type-specific deconvolution analysis showed enrichment of key biological processes in oligodendrocytes including myelination, axon ensheathment, glial cell development, and oligodendrocyte development. Conclusions: Collectively, these results show for the first time that glyphosate infiltrates the brain, elevates both the expression of TNFα and soluble Aβ, and disrupts the transcriptome in a dose-dependent manner, suggesting that exposure to this herbicide may have detrimental outcomes regarding the health of the general population.
2024-01-15 | GSE253299 | GEO
Project description:BackgroundHerbicides are environmental contaminants that have gained much attention due to the potential hazards they pose to human health. Glyphosate, the active ingredient in many commercial herbicides, is the most heavily applied herbicide worldwide. The recent rise in glyphosate application to corn and soy crops correlates positively with increased death rates due to Alzheimer's disease and other neurodegenerative disorders. Glyphosate has been shown to cross the blood-brain barrier in in vitro models, but has yet to be verified in vivo. Additionally, reports have shown that glyphosate exposure increases pro-inflammatory cytokines in blood plasma, particularly TNFα.MethodsHere, we examined whether glyphosate infiltrates the brain and elevates TNFα levels in 4-month-old C57BL/6J mice. Mice received either 125, 250, or 500 mg/kg/day of glyphosate, or a vehicle via oral gavage for 14 days. Urine, plasma, and brain samples were collected on the final day of dosing for analysis via UPLC-MS and ELISAs. Primary cortical neurons were derived from amyloidogenic APP/PS1 pups to evaluate in vitro changes in Aβ40-42 burden and cytotoxicity. RNA sequencing was performed on C57BL/6J brain samples to determine changes in the transcriptome.ResultsOur analysis revealed that glyphosate infiltrated the brain in a dose-dependent manner and upregulated TNFα in both plasma and brain tissue post-exposure. Notably, glyphosate measures correlated positively with TNFα levels. Glyphosate exposure in APP/PS1 primary cortical neurons increases levels of soluble Aβ40-42 and cytotoxicity. RNAseq revealed over 200 differentially expressed genes in a dose-dependent manner and cell-type-specific deconvolution analysis showed enrichment of key biological processes in oligodendrocytes including myelination, axon ensheathment, glial cell development, and oligodendrocyte development.ConclusionsCollectively, these results show for the first time that glyphosate infiltrates the brain, elevates both the expression of TNFα and soluble Aβ, and disrupts the transcriptome in a dose-dependent manner, suggesting that exposure to this herbicide may have detrimental outcomes regarding the health of the general population.
| S-EPMC9331154 | biostudies-literature
Project description: Not available
| S-EPMC10792902 | biostudies-literature
Project description:Glyphosate (GLY) is an effective antimetabolite that acts against the shikimate pathway 5-enolpyruvylshikimate 3-phosphate (EPSP) synthase, However, little is known about the genome-scale transcriptional responses of bacteria after glyphosate shock. To investigate further the mechanisms by which E. coli response to a glyphosate shock, a DNA-based microarray was used for transcriptional analysis of E. coli exposed to 200 mM glyphosate. RNA extracted from cells of E. coli K-12 JM109 cells after 4 h of growth to OD600 achieve 0.4, or cells after 200 mM glyphosate shock for 1 h when their OD600 achieved 0.4.
2011-07-21 | E-GEOD-30838 | biostudies-arrayexpress
Project description:Glyphosate (GLY) is an effective antimetabolite that acts against the shikimate pathway 5-enolpyruvylshikimate 3-phosphate (EPSP) synthase, However, little is known about the genome-scale transcriptional responses of bacteria after glyphosate shock. To investigate further the mechanisms by which E. coli response to a glyphosate shock, a DNA-based microarray was used for transcriptional analysis of E. coli exposed to 200 mM glyphosate.
2011-07-22 | GSE30838 | GEO
Project description:Control, TNFα and TNFα+JNK I treated GSCs
| PRJNA799754 | ENA
Project description:Despite all debates about its safe use, glyphosate still is the most widely applied active ingredient in herbicide products with renewed approval in the European Union until 2033. Non-target organisms are commonly exposed to glyphosate as a matter of its mode of application, with its broader environmental and biological impacts remaining under investigation. Glyphosate displays structural similarity to phosphoenolpyruvate (PEP), thereby competitively inhibiting the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), crucial for the synthesis of aromatic amino acids in plants, fungi, bacteria, and archaea. The majority of microbes, including the gut bacterium Escherichia coli (E. coli), possess a glyphosate-sensitive class I EPSPS, making them vulnerable to glyphosate's effects. Yet, little is known about glyphosate’s interactions with other bacterial proteins or its broader modes of action at the proteome level. Here, we employed a quantitative proteomics and thermal proteome profiling (TPP) approach, to identify novel protein binding partners of glyphosate in the E. coli proteome. Glyphosate exposure significantly altered amino acid synthesizing pathways, including increased abundance in shikimate pathway proteins, suggesting a compensatory mechanism. Extracellular riboflavin concentrations were elevated upon glyphosate exposure, while intracellular levels remained stable. Thermal proteome profiling indicated an effect of glyphosate on the thermal stability of certain proteins beyond the target enzyme EPSPS, including AroH and ProA. An elevated structural similarity between the substrates of the interaction candidates and glyphosate, similar to the competitive binding between PEP and glyphosate at the EPSPS, could be a reason for their interaction with the herbicide. Overall, glyphosate induced metabolic disturbances in E. coli, extending beyond its primary target, thereby providing new insights into glyphosate's broader impact on microbial systems.
2025-01-02 | PXD055134 | Pride
Project description:Glyphosate is one of the most widely used herbicides globally. It acts by inhibiting an enzyme in an aromatic amino synthesis pathway specific to plants and microbes, leading to view that glyphosate poses no risk to other organisms. However, there is growing concern that glyphosate is associated with detrimental health effects in humans, and an ever-increasing body of evidence suggests that glyphosate affects other animals including pollinating insects such as bees. Although pesticides have long been considered a contributing factor in the decline of wild bee populations most research on bees has focussed on demonstrating and understanding the effects (particularly sublethal ones) of insecticides. To assess whether glyphosate poses a potential risk to bees we characterised the changes in survival, behaviour, digestive tract proteome and microbiome in the bumblebee Bombus terrestris after chronic exposure to field relevant doses of glyphosate alone and as part of the commercially available product RoundUp Optima+®. Regardless of source, changes in response to herbicide exposure in important cellular and physiological processes in the digestive tract of B. terrestris were observed, with the abundances of proteins associated with oxidative stress regulation, metabolism, cellular adhesion, the extracellular matrix, and various signalling pathways being altered. Interestingly, endocytosis, oxidative phosphorylation, the TCA cycle, and carbohydrate, lipid, and amino acid metabolism were differentially altered depending on whether the exposure source was glyphosate AI or RoundUp Optima+®. In addition, RoundUp Optima+®, but not the active ingredient glyphosate, impacted fungal diversity in the digestive tract microbiota. Our research provides new insights into the potential mode of action and consequences of glyphosate exposure at the molecular and cellular levels in bumblebees and highlights issues with current regulatory measures involving commercial formulations of pesticides where the impact of the co-formulants on non-target organisms are generally overlooked.
2023-07-01 | PXD036578 | Pride
Project description:Transcriptomic profiling of glyphosate-treated seedlings comparing Arabidopsis wild-type (Ler) versus gcn2 mutant line
2015-03-10 | GSE56146 | GEO
Project description:This submission contains the RNAseq data from a study of leafy spurge crown buds transitioning through a seasonal dormancy time course following glyphosate treatments where buds transitioned from paradoprmancy to endodormancy and then to ecodormancy. The sequences in this study were mapped to an assembled transcriptome built from sequences from this study along with sequences from : 1) A study of leafy spurge crown buds through a time course for paradormancy release induced by excision of the aerial portion of the shoot (Series GSE71317). 2) A study identical to this study but where leafy spurge plants were not treated with glyphosate (Series GSE71321). 3) A previously submitted study of leafy spurge shoots following treament with glyphosate was also used to assemble the transcriptome (Series GSE56509). This crown buds transitioning through a seasonal dormancy time course following a glyphosate treatment study has 4 biological replicates collected at each of the three dormancy states (paradormant, endodormant, and ecodormant).
2015-08-05 | E-GEOD-71406 | biostudies-arrayexpress