The herbicide glyphosate inhibits hippocampal long-term potentiation and learning through activation of pro-inflammatory signaling
Abstract Glyphosate, a herbicide marketed as Roundup, is widely used but there are concerns this exposure could impair cognitive function. In the CA1 region of rat hippocampal slices, we investigated whether glyphosate alters synaptic transmission and long-term potentiation (LTP), a cellular model o...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-10-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-44121-7 |
| _version_ | 1797452690906677248 |
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| author | Yukitoshi Izumi Kazuko A. O’Dell Charles F. Zorumski |
| author_facet | Yukitoshi Izumi Kazuko A. O’Dell Charles F. Zorumski |
| author_sort | Yukitoshi Izumi |
| collection | DOAJ |
| description | Abstract Glyphosate, a herbicide marketed as Roundup, is widely used but there are concerns this exposure could impair cognitive function. In the CA1 region of rat hippocampal slices, we investigated whether glyphosate alters synaptic transmission and long-term potentiation (LTP), a cellular model of learning and memory. Our hypothesis is that glyphosate alters neuronal function and impairs LTP induction via activation of pro-inflammatory processes. Roundup depressed excitatory synaptic potentials(EPSPs) in a dose-dependent manner with complete suppression at 2000 mg/L. At concentrations ≤ 20 mg/L Roundup did not affect basal transmission, but 4 mg/L Roundup administered for 30 min inhibited LTP induction. Acute administration of 10–100 μM glyphosate also inhibited LTP induction. Minocycline, an inhibitor of microglial activation, and TAK-242, an inhibitor of toll-like receptor 4 (TLR4), both overcame the inhibitory effects of 100 µM glyphosate. Similarly, lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS), a different TLR4 antagonist, overcame the inhibitory effects. In addition, ISRIB (integrated stress response inhibitor) and quercetin, an inhibitor of endoplasmic reticulum stress, overcame the inhibitory effects. We also observed that in vivo glyphosate injection (16.9 mg/kg i.p.) impaired one-trial inhibitory avoidance learning. This learning deficit was overcome by TAK-242. These observations indicate that glyphosate can impair cognitive function through pro-inflammatory signaling in microglia. |
| first_indexed | 2024-03-09T15:12:18Z |
| format | Article |
| id | doaj.art-f9186c94def0462eb135470f80baaa46 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T15:12:18Z |
| publishDate | 2023-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-f9186c94def0462eb135470f80baaa462023-11-26T13:21:26ZengNature PortfolioScientific Reports2045-23222023-10-0113111210.1038/s41598-023-44121-7The herbicide glyphosate inhibits hippocampal long-term potentiation and learning through activation of pro-inflammatory signalingYukitoshi Izumi0Kazuko A. O’Dell1Charles F. Zorumski2Department of Psychiatry, Washington University School of MedicineDepartment of Psychiatry, Washington University School of MedicineDepartment of Psychiatry, Washington University School of MedicineAbstract Glyphosate, a herbicide marketed as Roundup, is widely used but there are concerns this exposure could impair cognitive function. In the CA1 region of rat hippocampal slices, we investigated whether glyphosate alters synaptic transmission and long-term potentiation (LTP), a cellular model of learning and memory. Our hypothesis is that glyphosate alters neuronal function and impairs LTP induction via activation of pro-inflammatory processes. Roundup depressed excitatory synaptic potentials(EPSPs) in a dose-dependent manner with complete suppression at 2000 mg/L. At concentrations ≤ 20 mg/L Roundup did not affect basal transmission, but 4 mg/L Roundup administered for 30 min inhibited LTP induction. Acute administration of 10–100 μM glyphosate also inhibited LTP induction. Minocycline, an inhibitor of microglial activation, and TAK-242, an inhibitor of toll-like receptor 4 (TLR4), both overcame the inhibitory effects of 100 µM glyphosate. Similarly, lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS), a different TLR4 antagonist, overcame the inhibitory effects. In addition, ISRIB (integrated stress response inhibitor) and quercetin, an inhibitor of endoplasmic reticulum stress, overcame the inhibitory effects. We also observed that in vivo glyphosate injection (16.9 mg/kg i.p.) impaired one-trial inhibitory avoidance learning. This learning deficit was overcome by TAK-242. These observations indicate that glyphosate can impair cognitive function through pro-inflammatory signaling in microglia.https://doi.org/10.1038/s41598-023-44121-7 |
| spellingShingle | Yukitoshi Izumi Kazuko A. O’Dell Charles F. Zorumski The herbicide glyphosate inhibits hippocampal long-term potentiation and learning through activation of pro-inflammatory signaling Scientific Reports |
| title | The herbicide glyphosate inhibits hippocampal long-term potentiation and learning through activation of pro-inflammatory signaling |
| title_full | The herbicide glyphosate inhibits hippocampal long-term potentiation and learning through activation of pro-inflammatory signaling |
| title_fullStr | The herbicide glyphosate inhibits hippocampal long-term potentiation and learning through activation of pro-inflammatory signaling |
| title_full_unstemmed | The herbicide glyphosate inhibits hippocampal long-term potentiation and learning through activation of pro-inflammatory signaling |
| title_short | The herbicide glyphosate inhibits hippocampal long-term potentiation and learning through activation of pro-inflammatory signaling |
| title_sort | herbicide glyphosate inhibits hippocampal long term potentiation and learning through activation of pro inflammatory signaling |
| url | https://doi.org/10.1038/s41598-023-44121-7 |
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