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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\u2019s disease and other neurodegenerative disorders. Glyphosate has been shown to cross the blood\u2013brain 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 TNF\u03b1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Here, we examined whether glyphosate infiltrates the brain and elevates TNF\u03b1 levels in 4-month-old C57BL\/6J mice. Mice received either 125, 250, or 500\u00a0mg\/kg\/day of glyphosate, or a vehicle via oral gavage for 14\u00a0days. Urine, plasma, and brain samples were collected on the final day of dosing for analysis via UPLC\u2013MS and ELISAs. Primary cortical neurons were derived from amyloidogenic APP\/PS1 pups to evaluate in vitro changes in A\u03b2\n                      <jats:sub>40-42<\/jats:sub>\n                      burden and cytotoxicity. RNA sequencing was performed on C57BL\/6J\u00a0brain samples to determine changes in the transcriptome.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our analysis revealed that glyphosate infiltrated the brain in a dose-dependent manner and upregulated TNF\u03b1 in both plasma and brain tissue post-exposure. Notably, glyphosate measures correlated positively with TNF\u03b1 levels. Glyphosate exposure in APP\/PS1 primary cortical neurons increases levels of soluble A\u03b2\n                      <jats:sub>40-42<\/jats:sub>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Collectively, these results show for the first time that glyphosate infiltrates the brain, elevates both the expression of TNF\u03b1 and soluble A\u03b2, 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12974-022-02544-5","type":"journal-article","created":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T21:37:36Z","timestamp":1658957856000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":81,"title":["Glyphosate infiltrates the brain and increases pro-inflammatory cytokine TNF\u03b1: implications for neurodegenerative disorders"],"prefix":"10.1186","volume":"19","author":[{"given":"Joanna K.","family":"Winstone","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khyatiben V.","family":"Pathak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Winslow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignazio S.","family":"Piras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ritin","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Huentelman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Pirrotte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon","family":"Velazquez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,7,28]]},"reference":[{"key":"2544_CR1","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1146\/annurev.publhealth.25.101802.123020","volume":"25","author":"MCR Alavanja","year":"2004","unstructured":"Alavanja MCR, Hoppin JA, Kamel F. 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