Roundup and glyphosate’s impact on GABA to elicit extended proconvulsant behavior in Caenorhabditis elegans
Abstract As 3 billion pounds of herbicides are sprayed over farmlands every year, it is essential to advance our understanding how pesticides may influence neurological health and physiology of both humans and other animals. Studies are often one-dimensional as the majority examine glyphosate by its...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-17537-w |
| _version_ | 1811285910285713408 |
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| author | Akshay S. Naraine Rebecca Aker Isis Sweeney Meghan Kalvey Alexis Surtel Venkatesh Shanbhag Ken Dawson-Scully |
| author_facet | Akshay S. Naraine Rebecca Aker Isis Sweeney Meghan Kalvey Alexis Surtel Venkatesh Shanbhag Ken Dawson-Scully |
| author_sort | Akshay S. Naraine |
| collection | DOAJ |
| description | Abstract As 3 billion pounds of herbicides are sprayed over farmlands every year, it is essential to advance our understanding how pesticides may influence neurological health and physiology of both humans and other animals. Studies are often one-dimensional as the majority examine glyphosate by itself. Farmers and the public use commercial products, like Roundup, containing a myriad of chemicals in addition to glyphosate. Currently, there are no neurological targets proposed for glyphosate and little comparison to Roundup. To investigate this, we compared how glyphosate and Roundup affect convulsant behavior in C. elegans and found that glyphosate and Roundup increased seizure-like behavior. Key to our initial hypothesis, we found that treatment with an antiepileptic drug rescued the prolonged convulsions. We also discovered over a third of nematodes exposed to Roundup did not recover from their convulsions, but drug treatment resulted in full recovery. Notably, these effects were found at concentrations that are 1,000-fold dilutions of previous findings of neurotoxicity, using over 300-fold less herbicide than the lowest concentration recommended for consumer use. Exploring mechanisms behind our observations, we found significant evidence that glyphosate targets GABA-A receptors. Pharmacological experiments which paired subeffective dosages of glyphosate and a GABA-A antagonist yielded a 24% increase in non-recovery compared to the antagonist alone. GABA mutant strain experiments showed no effect in a GABA-A depleted strain, but a significant, increased effect in a glutamic acid decarboxylase depleted strain. Our findings characterize glyphosate’s exacerbation of convulsions and propose the GABA-A receptor as a neurological target for the observed physiological changes. It also highlights glyphosate’s potential to dysregulate inhibitory neurological circuits. |
| first_indexed | 2024-04-13T02:50:59Z |
| format | Article |
| id | doaj.art-0291f5e12f0d46fc86af0c49c1a4355b |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T02:50:59Z |
| publishDate | 2022-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-0291f5e12f0d46fc86af0c49c1a4355b2022-12-22T03:05:50ZengNature PortfolioScientific Reports2045-23222022-08-0112111110.1038/s41598-022-17537-wRoundup and glyphosate’s impact on GABA to elicit extended proconvulsant behavior in Caenorhabditis elegansAkshay S. Naraine0Rebecca Aker1Isis Sweeney2Meghan Kalvey3Alexis Surtel4Venkatesh Shanbhag5Ken Dawson-Scully6Department of Biological Sciences, Florida Atlantic UniversityDepartment of Biological Sciences, Florida Atlantic UniversityDepartment of Biological Sciences, Florida Atlantic UniversityDepartment of Biological Sciences, Florida Atlantic UniversityDepartment of Biological Sciences, Florida Atlantic UniversityDepartment of Chemistry and Physics, Halmos College of Arts and Sciences, Nova Southeastern UniversityDepartment of Biological Sciences, Florida Atlantic UniversityAbstract As 3 billion pounds of herbicides are sprayed over farmlands every year, it is essential to advance our understanding how pesticides may influence neurological health and physiology of both humans and other animals. Studies are often one-dimensional as the majority examine glyphosate by itself. Farmers and the public use commercial products, like Roundup, containing a myriad of chemicals in addition to glyphosate. Currently, there are no neurological targets proposed for glyphosate and little comparison to Roundup. To investigate this, we compared how glyphosate and Roundup affect convulsant behavior in C. elegans and found that glyphosate and Roundup increased seizure-like behavior. Key to our initial hypothesis, we found that treatment with an antiepileptic drug rescued the prolonged convulsions. We also discovered over a third of nematodes exposed to Roundup did not recover from their convulsions, but drug treatment resulted in full recovery. Notably, these effects were found at concentrations that are 1,000-fold dilutions of previous findings of neurotoxicity, using over 300-fold less herbicide than the lowest concentration recommended for consumer use. Exploring mechanisms behind our observations, we found significant evidence that glyphosate targets GABA-A receptors. Pharmacological experiments which paired subeffective dosages of glyphosate and a GABA-A antagonist yielded a 24% increase in non-recovery compared to the antagonist alone. GABA mutant strain experiments showed no effect in a GABA-A depleted strain, but a significant, increased effect in a glutamic acid decarboxylase depleted strain. Our findings characterize glyphosate’s exacerbation of convulsions and propose the GABA-A receptor as a neurological target for the observed physiological changes. It also highlights glyphosate’s potential to dysregulate inhibitory neurological circuits.https://doi.org/10.1038/s41598-022-17537-w |
| spellingShingle | Akshay S. Naraine Rebecca Aker Isis Sweeney Meghan Kalvey Alexis Surtel Venkatesh Shanbhag Ken Dawson-Scully Roundup and glyphosate’s impact on GABA to elicit extended proconvulsant behavior in Caenorhabditis elegans Scientific Reports |
| title | Roundup and glyphosate’s impact on GABA to elicit extended proconvulsant behavior in Caenorhabditis elegans |
| title_full | Roundup and glyphosate’s impact on GABA to elicit extended proconvulsant behavior in Caenorhabditis elegans |
| title_fullStr | Roundup and glyphosate’s impact on GABA to elicit extended proconvulsant behavior in Caenorhabditis elegans |
| title_full_unstemmed | Roundup and glyphosate’s impact on GABA to elicit extended proconvulsant behavior in Caenorhabditis elegans |
| title_short | Roundup and glyphosate’s impact on GABA to elicit extended proconvulsant behavior in Caenorhabditis elegans |
| title_sort | roundup and glyphosate s impact on gaba to elicit extended proconvulsant behavior in caenorhabditis elegans |
| url | https://doi.org/10.1038/s41598-022-17537-w |
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