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Continuous low-level dietary exposure to glyphosate elicits dose and sex-dependent synaptic and microglial adaptations in the rodent brain.
2024
Cresto, Noemie | Courret, Margot | Génin, Athénaïs | Pauline Martin, Céline Marie | Bourret, Julie | Sakkaki, Sophie | de Bock, Frederic | Janvier, Alicia | Polizzi, Arnaud | Payrastre, Laurence | Ellero-Simatos, Sandrine | Audinat, Etienne | Perroy, Julie | Marchi, Nicola | Institut de Génomique Fonctionnelle (IGF) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM) | ToxAlim (ToxAlim) ; Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT) ; Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN) ; Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | IRCER - Axe 1 : procédés céramiques (IRCER-AXE1) ; Institut de Recherche sur les CERamiques (IRCER) ; Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut Matériaux Procédés Environnement Ouvrages (IMPEO) ; Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut Matériaux Procédés Environnement Ouvrages (IMPEO) ; Université de Limoges (UNILIM)-Université de Limoges (UNILIM) | Toxicologie Intégrative & Métabolisme (ToxAlim-TIM) ; ToxAlim (ToxAlim) ; Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT) ; Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN) ; Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT) ; Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN) ; Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | ANR-19-CE34-0007,GLYFLORE,Impact of a chronic dietary exposure to low-doses of glyphosate on the gut microbiota and microbiota-associated physiological functions (metabolism, intestinal immunity, brain structures and behavior)(2019) | ANR-17-CE34-0005,HepatoBrain,Mélange de pesticides et axe foie-cerveau : implication des récepteurs aux xénobiotiques(2017) | ANR-22-CE17-0061,CEST-Focus,Biomarqueurs de type CEST pour délimiter la zone épileptique(2022) | ANR-19-CE16-0018,MicroSENSO,Les microglies dans l'assemblage des circuits inhibiteurs pendant les périodes critiques sensorielles(2019) | ANR-21-CE17-0031,EPI-CATCHER,Nouvelles modalités d'imagerie et de spectroscopie GABA pour localiser la zone épileptique(2021)
International audience | Prolonged exposure to low levels of dietary contaminants is a context in modern life that could alter organ physiology gradually. Here, we aimed to investigate the impact of continuous exposure to acceptable daily intake (ADI) and non-observable adverse effect level (NOAEL) of glyphosate from gestation to adulthood using C57BL/6J mice and incorporating these levels into their food pellets. From adulthood, we analyzed neurophysiological and neuro-glia cellular adaptations in male and female animals. Using ex-vivo hippocampal slice electrophysiology, we found a reduced efficacy of Schaffer collateral-to-CA1 excitatory synapses in glyphosate-exposed dietary conditions, with ADI and NOAEL dose-dependent effects. Short-term facilitation of excitatory synaptic transmission was specifically increased in NOAEL conditions, with a predominant influence in males, suggesting a reduced probability of neurotransmitter release. Long-term synaptic potentiation (LTP) was decreased in NOAEL-exposed mice. Next, we explore whether these neurophysiological modifications are associated with neuro-glia changes in the somatosensory cortex and hippocampus. High-resolution confocal microscopy analyses unveil a dose-dependent increased density of excitatory Vglut1+ Homer1+ synapses. Microglial Iba1+ cells displayed a shortening of their ramifications, a sign of cellular reactivity that was more pronounced in males at NOAEL levels. The morphology of GFAP+ astrocytes was generally not modified. Finally, we asked whether mouse-specific cross-correlations exist among all data sets generated. This examination included the novel object recognition (NOR) test performed before ex vivo functional and immunohistochemical examinations. We report a negative linear regression between the number of synapses and NOR or LTP maintenance when plotting ADI and NOAEL datasets. These results outline synaptic and microglial cell adaptations resulting from prenatal and continuous dietary low levels of glyphosate, discernible in, but not limited to, adult males exposed to the NOAEL. We discuss the significance of these findings to real-world consumer situations and long-term brain resilience.
Show more [+] Less [-]Quinolone distribution, trophodynamics, and human exposure risk in a transit-station lake for water diversion in east China
2022
Liu, Yuanyuan | Hua, Zulin | Lü, Ying | Gu, Li | Luan, Chengmei | Li, Xiaoqing | Wu, Jianyi | Chu, Kejian
Quinolone antibiotics (QNs) pollution in lake environments is increasingly raising public concern due to their potential combined toxicity and associated risks. However, the spatiotemporal distribution and trophodynamics of QNs in transit-station lakes for water diversion are not well documented or understood. In this study, a comprehensive investigation of QNs in water, sediment, and aquatic fauna, including norfloxacin (NOR), ciprofloxacin (CIP), enrofloxacin (ENR), and ofloxacin (OFL), was conducted in Luoma Lake, a major transit station for the eastern route of the South-to-North Water Diversion Project in China. The target QNs were widely distributed in the water (∑QNs: 70.12 ± 62.79 ng/L) and sediment samples (∑QNs: 13.35 ± 10.78 ng/g dw) in both the non-diversion period (NDP) and the diversion period (DP), where NOR and ENR were predominant. All the QNs were detected in all biotic samples in DP (∑QNs: 80.04 ± 20.59 ng/g dw). The concentration of ∑QNs in the water in NDP was significantly higher than those in DP, whereas the concentration in the sediments in NDP was comparable to those in DP. ∑QNs in the water-sediment system exhibited decreasing trends from northwest (NW) to southeast (SE) in both periods; however, the Kₒc (organic carbon normalized partition coefficients) of individual QNs in DP sharply rose compared with those in NDP, which indicated that water diversion would alter the environmental fate of QNs in Luoma Lake. In DP, all QNs, excluding NOR, were all biodiluted across the food web; whereas their bioaccumulation potentials in the SE subregion were higher than those in the NW subregion, which was in contrast to the spatial distribution of their exposure concentrations. The estimated daily QN intakes via drinking water and aquatic products suggested that residents in the SE side were exposed to greater health risks, despite less aquatic pollution in the region.
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