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Chargé(e) de recherche
Faculté des Sciences et Technologies - Nancy
Université de Lorraine
03 72 74 57 66 | Nathalie.Grova@univ-lorraine.fr
Toxics, 10 (4), pp. 180.
Morel, C., Christophe, A., Maguin Gaté, K., Paoli, J., Turner, J.D., Schroeder, H., Grova, N.
Frontiers in Genetics Epigenomics and Epigenetics, 657171 (1), pp. 1-13.
Fernandes, S.B., Grova, N., Roth, S., Duca, R.D., Godderis, L., Guebels, P., Mérieux, S., Lumley, A.I., Bouillaud-Kremarik, P., Ernens, I., Devaux, Y., Schroeder, H., Turner, J.D.
DNA methylation is one of the most important epigenetic modifications and is closely related with several biological processes such as regulation of gene transcription and the development of non-malignant diseases. The prevailing dogma states that DNA methylation in eukaryotes occurs essentially through 5-methylcytosine but recently adenine methylation was also found to be present in eukaryotes. In mouse embryonic stem cells, 6-methyladenine was associated with the repression and silencing of genes, particularly in the X-chromosome, known to play an important role in cell fate determination. Here, we have demonstrated that 6mA is a ubiquitous eukaryotic epigenetic modification that is put in place during epigenetically sensitive periods such as embryogenesis and foetal development. In somatic cells there are clear tissue specificity in 6mA levels, with the highest 6mA levels being observed in the brain. In zebrafish, during the first 120h of embryo development, from a single pluripotent cell to an almost fully formed individual, 6mA levels steadily increase. An identical pattern was observed over embryonic days 7-21 in the mouse. Furthermore, exposure to a neurotoxic environmental pollutant during the same early life period may led to a decrease in the levels of this modification in female rats. The identification of the periods during which 6mA epigenetic marks are put in place increases our understanding of this mammalian epigenetic modification, and raises the possibility that it may be associated with developmental processes.
Toxics, 9 (50), pp. 1-18.
Saber Cherif, L., Cao-Lei, L., Farinelle, S., Muller, C.P., Turner, J.T., Schroeder, H., Grova, N.
The potent neurotoxicity of benzo[a]pyrene (B[a]P) has been suggested to be a susceptibility factor accelerating the onset of brain tumours and the emergence of neurobehavioural disturbances. B[a]P has been shown to be neurotoxic, acting directly on both the central and peripheral nervous systems, as well as indirectly via peripheral organs like liver and gut. By using a realistic B[a]P exposure scenario (0.02–200 mg/kg/day, 10 days) in mice, we elucidated brain-specific B[a]P metabolism and at identified hydroxylated B[a]P metabolites in serum which could be used as markers of cognitive impairment. Repeated oral administration of B[a]P led to, at the doses of 20 and 200 mg/kg/day, significant overexpression of Cyp1a1/Cyp1b1 in 2 out of the 3 brain regions considered, thereby suggesting the ability of the brain to metabolize B[a]P itself. At the same doses, mice exhibited a reduction in anxiety in both the elevated plus maze and the hole board apparatus. Concomitantly, B[a]P triggered dose-dependent changes in Nmda subunit expression (Nr1 and Nr2a/Nr2b) in areas involved in cognition. We detected 9-OH-B[a]P and 7,8-diol-B[a]P in serum at the level for which cognitive impairment was observed. We suggest that these metabolites may, in the future be exploited as potent biomarkers of B[a]P-induced cognitive impairments.
Journal of chromatography A, 1612, 460648
Grova, N., Wang, X., Hardy, E.M., Palazzi, P., Chata, C., Appenzeller, B.M.R.
Hair is increasingly used as a biological matrix of interest for the assessment of hormone secretion over extended periods of time. This study described the development and the validation of a sensitive UPLC-MS/MS method for simultaneous analysis of steroid and thyroid hormones in human hair. The gradient designed in this method enables to obtain a satisfactory separation of 9 hormones of interest: cortisol, cortisone, THE, THF, α-THF, triiodothyronine (T3) and thyroxine (T4), estradiol, and testosterone. Several methodological parameters of extraction (such as the used of “cut hair” versus “pulverized hair”, the extraction time, the incubation solvent purification on SPE column and hydrolysis) that may influence the determination of hormones levels in human hair, have thus been tested here. Therefore, the results obtained highlighted the necessity of using a C18 SPE purification method for the determination of both steroid and thyroid hormones in hair. This method allows reaching suitable levels of sensitivity for cortisol and cortisone since the results obtained pointed out concentration levels of cortisol in hair of volunteers similar to those observed in the literature. This method could also offer an important impact in the field of hormone analysis since it allows, for the first time, the quantification of both T3 and T4 in human hair.
International Journal of Molecular Sciences, 21 (14), pp. 5094-5104.
Holuka, C., Merz, M., Fernandes, S.B., Charalambous, E.G., Seal, S.V., Grova, N., Turner, J.D.
A poor socioeconomic environment and social adversity are fundamental determinants of human life span, well-being and health. Previous influenza pandemics showed that socioeconomic factors may determine both disease detection rates and overall outcomes, and preliminary data from the ongoing coronavirus disease (COVID-19) pandemic suggests that this is still true. Over the past years it has become clear that early-life adversity (ELA) plays a critical role biasing the immune system towards a pro-inflammatory and senescent phenotype many years later. Cytotoxic T-lymphocytes (CTL) appear to be particularly sensitive to the early life social environment. As we understand more about the immune response to SARS-CoV-2 it appears that a functional CTL (CD8+) response is required to clear the infection and COVID-19 severity is increased as the CD8+ response becomes somehow diminished or exhausted. This raises the hypothesis that the ELA-induced pro-inflammatory and senescent phenotype may play a role in determining the clinical course of COVID-19, and the convergence of ELA-induced senescence and COVID-19 induced exhaustion represents the worst-case scenario with the least effective T-cell response. If the correct data is collected, it may be possible to separate the early life elements that have made people particularly vulnerable to COVID-19 many years later. This will, naturally, then help us identify those that are most at risk from developing the severest forms of COVID-19. In order to do this, we need to recognize socioeconomic and early-life factors as genuine medically and clinically relevant data that urgently need to be collected. Finally, many biological samples have been collected in the ongoing studies. The mechanisms linking the early life environment with a defined later-life phenotype are starting to be elucidated, and perhaps hold the key to understanding inequalities and differences in the severity of COVID-19.
Archives of Toxicology, 93 (10), pp. 2849-2862.
Chata, C., Palazzi, P., Grova, N., Haan, S., Emond, C., Vaillant, M., Appenzeller, B.M.R.
Human biomonitoring provides information about chemicals measured in biological matrices, but their interpretation remains uncertain because of pharmacokinetic (PK) interactions. This study examined the PKs in blood from Long-Evans rats after a single oral dose of 0.4 mg/kg bw of each pesticide via a mixture of the 17 pesticides most frequently measured in humans. These pesticides are β-endosulfan; β-hexachlorocyclohexane [β-HCH]; γ-hexachlorocyclohexane [γ-HCH]; carbofuran; chlorpyrifos; cyhalothrin; cypermethrin; diazinon; dieldrin; diflufenican; fipronil; oxadiazon; pentachlorophenol [PCP]; permethrin; 1,1-dichloro-2,2bis(4-chlorophenyl)ethylene [p,p'-DDE]; 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane [p,p'-DDT]; and trifluralin. We collected blood at 10 min to 48-h timepoints in addition to one sample before gavage (for a control). We used GS-MS/MS to measure the pesticide (parents and major metabolites) concentrations in plasma, determined the PK parameters from 20 sampling timepoints, and analyzed the food, litter, and cardboard in the rats' environment for pesticides. We detected many parents and metabolites pesticides in plasma control (e.g., diethyl phosphate [DEP]; PCP; 3-phenoxybenzoic acid [3-PBA]; 3,5,6-trichloro-2-pyridinol [TCPy], suggesting pre-exposure contamination. The PK values post-exposure showed that the AUC0-∞ and Cmax were highest for TCPy and PCP; β-endosulfan, permethrin, and trifluralin presented the lowest values. Terminal T1/2 and MRT for γ-HCH and β-HCH ranged from 74.5 h to 117.1 h; carbofuran phenol presented the shortest values with 4.3 h and 4.8 h. These results present the first PK values obtained through a realistic pattern applied to a mixture of 17 pesticides to assess exposure. This study also highlights the issues of background exposure and the need to work with a relevant mixture found in human matrices.
International Journal of Genomics, doi.org/10.1155/2019/2085496
Grova, N., Schroeder, H., Olivier, J.-L., Tuner, J.D.
The incidence of neurodevelopmental and neurodegenerative diseases worldwide has dramatically increased over the last decades. Although the aetiology remains uncertain, evidence is now growing that exposure to persistent organic pollutants during sensitive neurodevelopmental periods such as early life may be a strong risk factor, predisposing the individual to disease development later in life. Epidemiological studies have associated environmentally persistent organic pollutant exposure to brain disorders including neuropathies, cognitive, motor, and sensory impairments; neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD); and neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS). In many ways, this expands the classical “Developmental Origins of Health and Disease” paradigm to include exposure to pollutants. This model has been refined over the years to give the current “three-hit” model that considers the individual’s genetic factors as a first “hit.” It has an immediate interaction with the early-life exposome (including persistent organic pollutants) that can be considered to be a second “hit.” Together, these first two “hits” produce a quiescent or latent phenotype, most probably encoded in the epigenome, which has become susceptible to a third environmental “hit” in later life. It is only after the third “hit” that the increased risk of disease symptoms is crystallised. However, if the individual is exposed to a different environment in later life, they would be expected to remain healthy. In this review, we examine the effect of exposure to persistent organic pollutants and particulate matters in early life and the relationship to subsequent neurodevelopmental and neurodegenerative disorders. The roles of those environmental factors which may affect epigenetic DNA methylation and therefore influence normal neurodevelopment are then evaluated.
Environmental Pollution, 255 (1), article 113171.
Le Goff, M., Lagadic-Gossmann, D., Latour, R., Podechard, N., Grova, N., Gauffre, F., Chevance, S., Burel, A., Appenzeller, B.M.R., Ulmann, L., Sergent, O., Le Ferrec, É.
Environmental contaminants, to which humans are widely exposed, cause or worsen several diseases, like cardiovascular diseases and cancers. Among these molecules, polycyclic aromatic hydrocarbons (PAHs) stand out since they are ubiquitous pollutants found in ambient air and diet. Because of their toxic effects, public Health agencies promote development of research studies aiming at increasing the knowledge about PAHs and the discovery of biomarkers of exposure and/or effects.
Extracellular vesicles (EVs), including small extracellular vesicles (S-EVs or exosomes) and large extracellular vesicles (L-EVs or microvesicles), are delivery systems for multimolecular messages related to the nature and status of the originating cells. Because they are produced by all cells and detected within body fluids, EV releases could act as cell responses and thereby serve as biomarkers.
Toxicological Sciences, 171 (2), pp. 443-462.
Van Meteren, N., Lagadic-Gossmann, D., Chevanne, M., Gallais, I., Gobart, D., Burel, A., Boucher, S., Bucher, S., Grova, N., Fromenty, B., Appenzeller, B.M.R., Chevance, S., Gauffre, F., Le Ferrec, É., Sergent, O.
Extracellular vesicles (EVs) are membrane-enclosed nanostructures released by cells into the extracellular environment. As major actors of physiological intercellular communication, they have been shown to be pathogenic mediators of several liver diseases. Extracellular vesicles also appear to be potential actors of drug-induced liver injury but nothing is known concerning environmental pollutants. We aimed to study the impact of polycyclic aromatic hydrocarbons (PAHs), major contaminants, on hepatocyte-derived EV production, with a special focus on hepatocyte death. Three PAHs were selected, based on their presence in food and their affinity for the aryl hydrocarbon receptor (AhR): benzo[a]pyrene (BP), dibenzo[a,h]anthracene (DBA), and pyrene (PYR). Treatment of primary rat and WIF-B9 hepatocytes by all 3 PAHs increased the release of EVs, mainly comprised of exosomes, in parallel with modifying exosome protein marker expression and inducing apoptosis. Moreover, PAH treatment of rodents for 3 months also led to increased EV levels in plasma. The EV release involved CYP metabolism and the activation of the transcription factor, the AhR, for BP and DBA and another transcription factor, the constitutive androstane receptor, for PYR. Furthermore, all PAHs increased cholesterol levels in EVs but only BP and DBA were able to reduce the cholesterol content of total cell membranes. All cholesterol changes very likely participated in the increase in EV release and cell death. Finally, we studied changes in cell membrane fluidity caused by BP and DBA due to cholesterol depletion. Our data showed increased cell membrane fluidity, which contributed to hepatocyte EV release and cell death.
Séminaire de l'école doctorale SIReNa, 26 mars, Dématérialisé
Morel, C., Christophe, A., Maguin-Gaté, K., Jubreaux, J., Degiorgio, C., Bouillaud-Kremarik, P., Grova, N., Schroeder, H.
Evidence is now growing that early-life environmental pollutant exposure during the critical period of brain development may be an important risk factor, contributing to the emergence of neurobehavioral disorders later in life (Grova et al., 2019). In this context, our team previously highlighted that a daily exposure of rat pups to the α isomer of HBCDD, a brominated flame retardant largely added to polystyrene building materials, during gestation and lactation (66 ng/kg/day) induced disturbances in locomotor maturation, exploratory activity and level of anxiety over the first 6 weeks of postnatal life (Maurice et al., 2015). The present study therefore aims at evaluating the developmental neurotoxicity of an early exposure to this chemical that is considered as a compound of high concern for human health, in comparison with valproic acid (VPA), a common anti-epileptic drug known to induce developmental disorders and contribute to the emergence of autism spectrum disorders. HBCDD-exposed dams were administered daily p.o. from GD0 to PND21 with 100 ng/kg/day of α-HBCDD isomer in oil, whereas the two other groups received the vehicle only. At GD12, VPA-treated rats received a single i.p. injection of VPA at a dose of 600 mg/kg whereas the two other groups were injected with the vehicle only. Pups were tested for their early behavioral development from PND3 to PND21 using a standardized test battery. At PND21, brains were collected and cortex removed for further analysis. The results pointed out the ability of both compounds to induce subtle significant behavioral changes during the neurodevelopment with the reduction in the time spent to grasp a rotating grid in VPA-exposed pups at PND9-11 and the increase in the time to move back in the neogative geotaxis task in the HBCDD-treated rats at PND8-10. No significant modification in the olfactory discriminative test (PN9-PND11) has been observed among groups. Cortical protein expression was analyzed for the neuroinflammation and synaptic plasticity, demonstrating a significant increase in the level of glial fibrillary acidic protein (GFAP) associated with a diminution of synaptophysin in the VPA-treated pups whereas HBCDD-exposed rats showed only an increasing level of expression of GFAP. In conclusion, both results suggest the ability of both compounds to impair slightly the brain and behavior development of rat pups in a different way according to the chemicals. The measurements of the cytochrome oxydase activity in various brain regions, currently under progress, should provide us additional information on the impact of an early exposure to HBCDD or VPA on behavioral impairments later in life.
26th International Symposium on Polycyclic Aromatic Compounds (ISPAC), 8-12 septembre, Örebro, Suède
Grova, N., Hardy, E.M., Appenzeller, B.M.R.
Urban air pollution is set to become the primary environmental cause of mortality worldwide by 2050. Nowadays substantial part of EU's population (more particularly sensitive or vulnerable people) remains exposed to levels of air pollution which exceed WHO recommendations. To ensure a healthy environment for all, local measures for reducing global PAH emissions should be completed with adequate policy at both national and EU level, including biomonitoring of human exposure to different types of PAH mixtures.
Significant efforts have recently been undertaken towards the development of efficient strategies for the assessment of human exposure to PAH. Alongside the analysis of urinary metabolites which are traditional biomarkers of PAH exposure, the possibility of detecting PAH metabolites in hair is to date clearly established. This unconventional matrix is not impacted by short-term variations in exposure - as can be observed with blood and urine - and therefore accurately represents an individual’s average level of exposure over time, which is the most relevant information when investigating possible linkages with biological effect. In this context, we developed a method based on GC-MS/MS for the analysis of 52 OH-PAH and 10 tetrahydroxylated forms in hair. Based on an animal experimental model, the relationship between the PAH exposure level and the resulting concentration of their metabolites in hair was investigated. Sixty-four adult female Long Evans rats were randomly allocated to experimental groups receiving 0.01 to 0.8 mg/kg body weight of a mixture of 13 PAH solubilized in vegetable oil, by oral administration, 3 times per week for 90 days. By widening the range of PAH metabolites used as biomarkers of exposure so as to include the analysis of B[a]P tetrahydroxylated forms and of the tetrahydroxylated metabolites of other PAH’s (especially those exhibiting more than 5 aromatic rings), these analyses will enable multi-exposure assessments which are more accurately representative of actual situations of exposure to these compounds and 2) evaluate the toxicity effect on human beings.
5th International Systems Biomedicine Symposium - Systems neuroscience: bridging the scales of the brain, 5 novembre, Esch-sur-Alzette, Luxembourg
Roth, S., Lamartinière, Y., Fernandes, S.B., Mériaux, S., Maguin Gaté, K., Guebels, P., Godderis, L., Duca, R.C., Bouillaud-Kremarik, P., Turner, J.D., Schroeder, H., Grova, N.
Short- and long-term behavioral impairments related to anxiety, sexual and social behavior have recently been demonstrated in rats daily exposed during gestation and lactation (GD0 to PND21) to α-hexabromocyclododecane (α-HBCDD, 66 ng/kg/day of body weight), a brominated flame retardant of very high concern. The present study is aimed at examining the effects of such exposure on the potent mechanism leading to the phenotypes observed in the cerebellum of male pups at PND14. This brain region is known for its high sensitivity to environmental disturbances occurring essentially during the early phase of brain development. In the cerebellum, we initially assumed that perinatal exposure to α-HBCDD may i) lead to epigenetic changes in the 6-methyl Adenine (6-mA), which has been identified as genuine epigenetic mark through different techniques (LC-MS/MS, DotBlot and immunochemistry) and ii) induce neuroinflammation which could also exert key influence in neuronal dysfunction. The results revealed that α-HBCDD is able to alter the expression levels of proteins associated with neuroinflammation such as GFAP (+10% compared with controls for males and -18% compared to controls for females) and S100β (+ 19% compared with controls in males, p<0.05) which could later interfere in brain development and functioning. Concomitantly, a decrease in males (-30%) in 6mA has been noticed in this part of the brain, suggesting the ability of this contaminant to induce early reduction in DNA methylation. Corresponding IlluminaR sequencing proved that many differential methylated regions (DMR) can be identified on the different chromosomes at PND14 with a particular attention to be paid to changes on the Y and mitochondrial chromosome. This early decrease in 6mA signal intensity was also observed in the cerebellum at the adult stage (PND270) for both female and male exposed animals compared with controls, with a significant interaction between HBCDD and sex (p<0.01). Detailed gene analysis, currently under evaluation, should enable us to understand how the impact of early life α-HBCDD exposure on gene expression induces chronic neuroinflammation and changes in neurotransmission pathways with the occurrence of behavioural impairments later in life as a consequence.
26th International Symposium on Polycyclic Aromatic Compounts (ISPAC), 08-12 septembre, Örebro, Suède
Morel, C., Schroeder, H., Paoli, J., Charalambous, E., Thiebault, C., Guebels, P., Dosen, A., Turner, J.D., Genay, M., Grova, N.
There is growing evidence that supplementation with probiotics improves intestinal transit,
induces systemic protective immune responses and presents beneficial effect on stress
and anxiety. Concomitantly, exposure to Polycyclic Aromatic Hydrocarbons (PAH),
especially in juvenile, proves to induce cognitive developmental delay and behavioral
impairments related to anxiety.
This study provides a proof of concept on the use of probiotic beneficial effect to
counteract the neurotoxic effects induced by PAH. It was carried out by using six groups
of 12 Swiss female mice each . Three groups were daily fed with a mixture of probiotics
for 8 weeks whereas the others received the vehicule only. After 1 month of probiotic
supplementation, the 3 groups of each conditions were exposed by oral gavage to a
mixture of 16-PAHs (3 times per week, 0, 20 and 200 µg/kg, 4 weeks). Neurobehavioural
status related to exploration, anxiety and immediate learning were studied during the last
week of PAH exposure. Faeces were collected, -before, -after 4 weeks of probiotic
supplementation and -at the end of PAH exposure to assess the microbiota balance and
the probiotic viability along the gastro-intestinal tract. Preliminary data showed that
probiotics enable a faster growth of mice compared to controls (p<0.05) and reduce the
loss of weight observed in PAH-treated groups. Enumeration of probiotic strains at several
time point, pointed out that the probiotics survive along the gastro-intestinal tract, but PAH
seems to affect their viability as well as this of microbiota at 200 µg/kg of bw. Analysis of
microbiota by 16S ribosomal RNA gene sequencing should confirm this result. In the lightdark
apparatus, supplementation with probiotics partially restore the decrease of the level
of activity observed in mice exposed to PAH 200 µg/kg (p<0.05). Behavioral analyses
currently under evaluation should enable us to understand how PAH-induced
neurotoxicity and if probiotics may prevent their detrimental effects.
17th biannual meeting of the International Neurotoxicology Association (INA-17) , 28 septembre - 3 octobre, Düsseldorf, Allemagne
Roth, S., Lamartinière, Y., Fernandes, S.B., Mériaux, S., Maguin Gaté, K., Guebels, P., Godderis, L., Duca, R.C., Bouillaud-Kremarik, P., Turner, J.D., Schroeder, H., Grova, N.
Short- and long-term behavioral impairments related to anxiety, sexual and social behavior have been recently demonstrated in rats daily exposed during gestation and lactation (GD0 to PND21) to α-hexabromocyclododecane (α-HBCDD, 66 ng/kg/day of body weight), a brominated flame retardant of very high concern. The present study aimed at examining the effects of such exposure on potent mechanism leading to the observed phenotypes in the cerebellum of male pups at PND14. This part of the brain is known as a structure of high sensitivity to environmental disturbances occurring during the early phase of brain development and of later maturation compared to other brain regions. In cerebellum, we assume that a perinatal exposure to α-HBCDD may i) lead to epigenetic changes of the 6-methyl Adenine (6-mA) that has been identified as genuine epigenetic mark through different techniques (LC-MS/MS, DotBlot and immunochemistry) and ii) induce neuroinflammation which could also play a key role in neuronal dysfunction. The results showed that α-HBCDD is able to change the expression levels of proteins associated to neuroinflammation such as GFAP (+10% compared to controls in male and -18% compared to control in females) and S100β (+ 19% compared to controls in male, p<0.05) which later on could interfere with brain development and functioning. Concomitantly, a decrease in male (-30%) in 6mA has been noticed in this part of the brain, suggesting the ability of this contaminant to induce an early reduction of DNA methylation. Corresponding IlluminaR sequencing proved that many differential methylated regions (DMR) can be identified on the different chromosomes at PND14 with a particular attention to be put on changes on the Y and mitochondrial chromosome. Results under progress showed that this early decrease in 6mA signal intensity was also stated in the cerebellum at the adult stage (PND270) for both female and male-exposed animals compared to controls with a significant interaction between HBCDD and sex (p<0.01). Detailed gene analysis, currently under evaluation, should enable us to understand how the impact of early life α-HBCDD exposure on gene expression may induce chronic neuroinflammation and changes in neurotransmission pathways with the occurrence of behavioural impairments later in life as a consequence.
Microbes – 15ème Congrès National de la Société Française de Microbiologie, 30 septembre - 2 octobre, Paris, France
Morel, C., Schroeder, H., Paoli, J., Charalambous, E., Thiebault, C., Guebels, P., Dosen, A., Turner, J.D., Genay, M., Grova, N.
Introduction and objectives:
There is growing evidence that supplementation with probiotics improves intestinal transit, induces systemic protective immune responses and presents beneficial effect on stress and anxiety. Concomitantly, exposure to Polycyclic Aromatic Hydrocarbons (PAH), especially in juvenile, proves to induce cognitive developmental delay and behavioral impairments related to anxiety. This study provides a proof of concept on the use of probiotic beneficial effect to counteract the neurotoxic effects induced by PAH.
Material and methods:
We studied six groups of 12 Swiss female mice each. Three groups were daily fed with a mixture of probiotics for 8 weeks whereas the others received the vehicule only. After 1 month of probiotic supplementation, the 3 groups of each conditions were exposed by oral gavage to a mixture of 16-PAHs (3 times per week, 0, 20 and 200 µg/kg, 4 weeks). Neurobehavioural status related to exploration, anxiety and immediate learning were studied during the last week of PAH exposure. Faeces were collected, -before, -after 4 weeks of probiotic supplementation and -at the end of PAH exposure to assess the microbiota balance and the probiotic viability along the gastro-intestinal tract.
Results, discussion, conclusion:
Preliminary data showed that probiotics enable a faster growth of mice compared to controls (p<0.05) and reduce the loss of weight observed in PAH-treated groups. Enumeration of probiotic strains at several time point, pointed out that the probiotics survive along the gastro-intestinal tract, but PAH seems to affect their viability as well as this of microbiota at 200 µg/kg of bw. Analysis of microbiota by 16S ribosomal RNA gene sequencing should confirm this result. In the light-dark apparatus, supplementation with probiotics partially restore the decrease of the level of activity observed in mice exposed to PAH 200 µg/kg (p<0.05). Behavioral analyses currently under evaluation should enable us to understand how PAH-induced neurotoxicity and if probiotics may prevent their detrimental effects.
