HAL du Programme national de recherche environnement-santé-travail (PNR EST)
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Did decades of glyphosate use have selected for resistant amphibians in agricultural habitats?
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CHARMM FFs parameterization for Flupyradifurone: an in-depth dive in the optimization maze!
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A qualitative approach to experiential knowledge identified in focus groups aimed at co-designing a provocation test in the study of electrohypersensitivity
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A Novel Reverberation Chamber for In Vitro Bioelectromagnetic Experiments at 3.5 GHz
No full textInternational audiencePrevious studies have shown that spontaneously active cultured networks of cortical neuron grown planar microelectrode arrays are sensitive to radiofrequency (RF) fields and exhibit an inhibitory response more pronounced as the exposure time and power increase. To better understand the mechanism behind the observed effects, we aimed at identifying similarities and differences between the inhibitory effect of RF fields (continuous wave, 1800 MHz) to the γ-aminobutyric acid type A (GABA A ) receptor agonist muscimol (MU). Inhibition of the network bursting activity in response to RF exposure became apparent at an SAR level of 28.6 W/kg and co-occurred with an elevation of the culture medium temperature of ~1°C. Exposure to RF fields preferentially inhibits bursting over spiking activity and exerts fewer constraints on neural network bursting synchrony, differentiating it from a pharmacological inhibition with MU. Network rebound excitation, a phenomenon relying on the intrinsic properties of cortical neurons, was observed following the removal of tonic hyperpolarization after washout of MU but not in response to cessation of RF exposure. This implies that hyperpolarization is not the main driving force mediating the inhibitory effects of RF fields. At the level of single neurons, network inhibition induced by MU and RF fields occurred with reduced action potential (AP) half-width. As changes in AP waveform strongly influence efficacy of synaptic transmission, the narrowing effect on AP seen under RF exposure might contribute to reducing network bursting activity. By pointing only to a partial overlap between the inhibitory hallmarks of these two forms of inhibition, our data suggest that the inhibitory mechanisms of the action of RF fields differ from the ones mediated by the activation of GABA A receptors
Residential proximity to croplands at birth and childhood leukaemia
No full textInternational audienceBackground: Domestic and parental occupational pesticide exposures are suspected of involvement in the occurrence of childhood acute leukaemia (AL), but the role of exposure to agricultural activities is little known. In a previous ecological study conducted in France, we observed an increase in acute lymphoblastic leukaemia (ALL) incidence rate with increasing viticulture density in the municipalities of residence at diagnosis.Objectives: This study aimed to test the hypothesis that residential proximity to croplands at birth increases the risk of childhood AL, with a particular focus on vineyards.Methods: We identified all the primary AL cases diagnosed before the age of 15 years in the cohorts of children born in the French municipalities between 1990 and 2015. We estimated crop densities in each municipality of residence at birth using agricultural census data, for ten crop types. Variations in standardized incidence ratios (SIR) were evaluated with Poisson regression models, for all AL, ALL and acute myeloid leukaemia (AML), separately.Results: Among the 19,809,700 children born and residing in mainland France at birth in 1990-2015, 8,747 AL cases (7,236 ALL and 1,335 AML) were diagnosed over the period. We did not evidence any statistically significant positive association between total crop density or any specific crop density in the municipality of residence at birth and all AL, ALL or AML. Interestingly, we observed a higher ALL incidence rate in the municipalities with the highest viticulture densities (SIR = 1.25 95%CI [1.01-1.54]). Adjusting for the main potential confounders did not change the results.Conclusion: Our study does not support the hypothesis that residential proximity to croplands, particularly vineyards, around birth plays a role in childhood leukaemia. The slightly higher ALL incidence rate in children born in the municipalities with the highest viticulture densities may reflect the previously-observed association at diagnosis
Golgipathies reveal the critical role of the sorting machinery in brain and skeletal development
No full textInternational audienceAssociation genetic studies and genome-scale CRISPR screens have recently identified ARF3 and TMEM251/LYSET/GCAF as Golgi-resident factors essential to brain and skeletal development. Here we discuss how even though the consequences of mutations in these genes affect endosomal and lysosomal compartments, the problem originates in the Golgi complex and may involve either the identity of the carrier vesicles or that of cargo molecules. 1234567890():,; 1234567890():,
Exposure to 1800 MHz LTE electromagnetic fields under proinflammatory conditions decreases the response strength and increases the acoustic threshold of auditory cortical neurons
No full textInternational audienceIncreased needs for mobile phone communications have raised successive generations (G) of wireless technologies, which could differentially affect biological systems. To test this, we exposed rats to single head-only exposure of a 4G long-term evolution (LTE)-1800 MHz electromagnetic field (EMF) for 2 h. We then assessed the impact on microglial space coverage and electrophysiological neuronal activity in the primary auditory cortex (ACx), under acute neuroinflammation induced by lipopolysaccharide. The mean specific absorption rate in the ACx was 0.5 W/kg. Multiunit recording revealed that LTE-EMF triggered reduction in the response strength to pure tones and to natural vocalizations, together with an increase in acoustic threshold in the low and medium frequencies. Iba1 immunohistochemistry showed no change in the area covered by microglia cell bodies and processes. In healthy rats, the same LTE-exposure induced no change in response strength and acoustic threshold. Our data indicate that acute neuroinflammation sensitizes neuronal responses to LTE-EMF, which leads to an altered processing of acoustic stimuli in the ACx
Inhibition of Autophagy Negates Radiofrequency-Induced Adaptive Response in SH-SY5Y Neuroblastoma Cells
No full textInternational audienceIn the last years, radiofrequency (RF) has demonstrated that it can reduce DNA damage induced by a subsequent treatment with chemical or physical agents in different cell types, resembling the adaptive response, a phenomenon well documented in radiobiology. Such an effect has also been reported by other authors both in vitro and in vivo, and plausible hypotheses have been formulated, spanning from the perturbation of the cell redox status, to DNA repair mechanisms, and stress response machinery, as possible cellular mechanisms activated by RF pre-exposure. These mechanisms may underpin the observed phenomenon, and require deeper investigations. The present study aimed to determine whether autophagy contributes to RF-induced adaptive response. To this purpose, SH-SY5Y human neuroblastoma cells were exposed for 20 h to 1950 MHz, UMTS signal, and then treated with menadione. The results obtained indicated a reduction in menadione-induced DNA damage, assessed by applying the comet assay. Such a reduction was negated when autophagy was inhibited by bafilomycin A1 and E64d. Moreover, CRISPR SH-SY5Y cell lines defective for ATG7 or ATG5 genes did not show an adaptive response. These findings suggest the involvement of autophagy in the RF-induced adaptive response in human neuroblastoma cells; although, further investigation is required to extend such observation at the molecular level
Exposure to a mixture of benzo[a]pyrene and triclosan induces multi-and transgenerational metabolic disorders associated with decreased female investment in reproduction in Silurana (Xenopus) tropicalis
No full textInternational audienceAnimals must partition limited resources between their own growth and subsequent reproduction. Endocrine disruptors (ED) may cause maternal metabolic disorders that decrease successful reproduction and might be responsible for multi- and transgenerational effects in amphibians. We found that the frog Silurana (Xenopus) tropicalis, exposed to environmentally relevant concentrations of benzo[a]pyrene and triclosan throughout its life cycle, produced F1 females with delayed sexual maturity and decreased size and weight. These F1 females displayed a marked metabolic syndrome associated with decreased fasting plasma cholesterol and triglyceride concentrations and decreased gonadal development. F1 females from F0 exposed animals also had decreased reproductive investment highlighted by a decrease of oocyte lipid reserves associated with significant F2-tadpole mortality. F2 females from F0 exposed animals also displayed a marked metabolic syndrome but were able to correctly direct liver lipid metabolism to the constitution of fat bodies and oocyte yolk stores. In addition, the F2 females produced progeny that had normal mortality levels at 5 days post hatching compared to the controls suggesting a good reproductive investment. Our data confirmed that these ED, at concentrations often found in natural ponds, can induce multi- and transgenerational metabolic disorders in the progeny of amphibians that are not directly exposed. We present a hypothesis to explain the transmission of the metabolic syndrome across generations through modification of egg reserves. However, when high mortality occurred at the tadpole stage, surviving females were able to cope with metabolic costs and produce viable progeny through sufficient investment in the contents of oocyte reserves
Personal exposure to PM2.5 oxidative potential and its association to birth outcomes
No full textInternational audienceBackground: Prenatal exposure to fine particulate matter (PM2.5) assessed through its mass concentration has been associated with foetal growth restriction in studies based on outdoor levels. Oxidative potential of PM2.5 (OP) is an emerging metric a priori relevant to mechanisms of action of PM on health, with very limited evidence to indicate its role on birth outcomes.Objectives: We investigated the association of OP with birth outcomes and compared it with that of PM2.5 mass concentration.Methods: 405 pregnant women from SEPAGES cohort (Grenoble area) carried PM2.5 personal dosimeters for one or two one-week periods. OP was measured using dithiothreitol (DTT) and ascorbic acid (AA) assays from the collected filters. Associations of each exposure metric with offspring weight, height, and head circumference at birth were estimated adjusting for potential confounders.Results: The correlation between PM2.5 mass concentration and [Formula: see text] was 0.7. An interquartile range increase in .. was associated with reduced weight (adjusted change, -64 g, -166 to -11, p = 0.02) and height (-4 mm, -6 to -1, p = 0.01) at birth. PM2.5 mass concentration showed similar associations with weight (-53 g, -99 to -8, p = 0.02) and height (-2 mm, -5 to 0, p = 0.05). In birth height models mutually adjusted for the two exposure metrics, the association with [Formula: see text] was less attenuated than that with mass concentration, while for weight both effect sizes attenuated similarly. There was no clear evidence of associations with head circumference for any metric, nor for [Formula: see text] with any growth parameter.Impact: PM2.5 pregnancy exposure assessed from personal dosimeters was associated with altered foetal growth. Personal OP exposure was associated with foetal growth restrictions, specifically decreased weight and height at birth, possibly to a larger extent than PM2.5 mass concentration alone. These results support OP assessed from DTT as being a health-relevant metric. Larger scale cohort studies are recommended to support our findings