Comparison of the effect of glyphosate and glyphosate-based herbicide on hippocampal neurogenesis after developmental exposure in rats. (1st January 2023)

• Record Type: Journal Article
• Authors: Ojiro, Ryota; Okano, Hiromu; Takahashi, Yasunori; Takashima, Kazumi; Tang, Qian; Ozawa, Shunsuke; Zou, Xinyu; Woo, Gye-Hyeong; Shibutani, Makoto
• Is Part Of: Toxicology. Volume 483(2023)
• Publication Date: 2023-01-01
• Subjects: AMPA alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid -- ANOVA analysis of variance -- ARC activity-regulated cytoskeleton-associated protein -- BDNF brain-derived neurotrophic factor -- BW body weight -- CALB1 calbindin-D-28 K -- CALB2 calbindin-D-29 K -- CD cluster of differentiation -- cDNA complementary DNA -- COX2 cyclooxygenase-2 -- CT threshold cycle -- DCX doublecortin -- DG dentate gyrus -- DNT developmental neurotoxicity -- FOS Fos proto-oncogene, AP-1 transcription factor subunit -- GABA γ-aminobutyric acid -- GAD67 glutamic acid decarboxylase 67 -- GBH glyphosate-based herbicide -- GCL granule cell layer -- GD gestational day -- GFAP glial fibrillary acidic protein -- GHSR growth hormone secretagogue receptor -- GlyP glyphosate -- Iba1 ionized calcium-binding adapter molecule 1 -- IEG immediate-early gene -- MDA malondialdehyde -- MT-I/II metallothionein-I/II -- NeuN neuronal nuclei -- NMDA N-methyl-D-aspartate -- NPC neural progenitor cell -- NSC neural stem cell -- OECD Organization for Economic Co-operation and Development -- p-ERK1/2 phosphorylated extracellular signal-regulated kinase 1/2 -- PCNA proliferating cell nuclear antigen -- PFA paraformaldehyde -- PND postnatal day -- PVALB parvalbumin -- RELN reelin -- RT reverse transcription -- SGZ subgranular zone -- SOX2 SRY-box transcription factor 2 -- SST somatostatin -- TBR2 T-box brain protein 2 -- TrkB tropomyosin receptor kinase B -- TUBB3 tubulin, beta 3 class III -- TUNEL terminal deoxynucleotidyl transferase dUTP nick end labeling; Glyphosate (GlyP) -- Glyphosate-based herbicide (GBH) -- Neurogenesis -- Oxidative stress -- Synaptic plasticity -- Rat; Toxicology -- Periodicals; Chemicals -- Physiological effect -- Periodicals; 615.9005
• DOI: 10.1016/j.tox.2022.153369
• Languages: English
• ISSNs: 0300-483X

Abstract

Abstract: Increasing evidence indicates that glyphosate (GlyP)-based herbicides (GBHs) induce developmental neurotoxicity. The present study investigated the developmental exposure effect of GlyP and GBH on hippocampal neurogenesis in rats. Dams were treated from gestational day 6 to day 21 post-delivery on weaning with a diet containing 1.5% or 3.0% GlyP or drinking water with 1.0% GBH (containing 0.36% GlyP). Dams in the 1.5%-GlyP, 3.0%-GlyP, and GBH groups received 1.04, 2.16, and 0.25 g GlyP/kg body weight (BW)/day during gestation, and 2.27, 4.65, and 0.58 g GlyP/kg BW/day during lactation, respectively. On weaning, 3.0% GlyP- and GBH-exposed offspring decreased the BW, and the latter also decreased the brain weight. Both compounds suppressed neural progenitor cell proliferation in the neurogenic niche, and GlyP-exposed offspring showed a decreased number of TUBB3 + immature granule cells. In contrast, both compounds increased the number of ARC + granule cells, suggesting increased synaptic plasticity. Both compounds downregulated antioxidant genes ( Cat and Sod2 ) in the dentate gyrus, suggestive of increased sensitivity to oxidative stress, which might be related to the suppression of neurogenesis. At the adult age, GBH alone sustained decreases in body and brain weights. Both compounds increased hippocampal malondialdehyde levels and upregulated Cat in the dentate gyrus, suggesting induction of oxidative stress. Both compounds upregulated Casp9, and GBH increased neural progenitor cell apoptosis, suggesting disruption of neurogenesis related to oxidative stress. GBH increased the number of COX2 + granule cells, and both compounds upregulated Arc, suggesting increased synaptic plasticity. These results suggest that GlyP and GBH might cause similar effects on disruption of neurogenesis accompanying compensatory responses and induction of oxidative stress responses through the adult age in the hippocampus. However, effects on adult age were more evident with GBH, suggesting that the surfactants contained in GBH might have contributed to the enhanced neurotoxicity of GlyP, similar to the enhanced general toxicity. Highlights: Glyphosate (GlyP) and GlyP-based herbicide (GBH) similarly suppressed neurogenesis. Effects were continued to the adult age accompanying compensatory responses. Both compounds also induced oxidative stress responses through the adult age. Neurotoxic effects were more evident with 1.0% GBH as compared to 3.0% GlyP. GBH surfactants might have contributed to the enhanced neurotoxicity of GlyP.