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Faculté des Sciences et Technologies - Nancy
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Toxics, 10 (4), pp. 180.
Morel, C., Christophe, A., Maguin Gaté, K., Paoli, J., Turner, J.D., Schroeder, H., Grova, N.
Nutrients, 14 (24), pp. 5338.
Pinchaud, K., Hafeez, Z., Auger, S., Chatel, J.-M., Chadi, S., Langella, P., Paoli, J., Dary-Mourot, A., Maguin-Gaté, K., Olivier, J.-L.
Although arachidonic acid (ARA) is the precursor of the majority of eicosanoids, its influence as a food component on health is not well known. Therefore, we investigated its impact on the gut microbiota and gut–brain axis. Groups of male BALB/c mice were fed either a standard diet containing 5% lipids (Std-ARA) or 15%-lipid diets without ARA (HL-ARA) or with 1% ARA (HL + ARA) for 9 weeks. Fatty acid profiles of all three diets were the same. The HL-ARA diet favored the growth of Bifidobacterium pseudolongum contrary to the HL + ARA diet that favored the pro-inflammatory Escherichia–Shigella genus in fecal microbiota. Dietary ARA intake induced 4- and 15-fold colic overexpression of the pro-inflammatory markers IL-1β and CD40, respectively, without affecting those of TNFα and adiponectin. In the brain, dietary ARA intake led to moderate overexpression of GFAP in the hippocampus and cortex. Both the hyperlipidic diets reduced IL-6 and IL-12 in the brain. For the first time, it was shown that dietary ARA altered the gut microbiota, led to low-grade colic inflammation, and induced astrogliosis in the brain. Further work is necessary to determine the involved mechanisms.
Oilseeds and fats, Crops and Lipids, 25 (4), pp. D406-D413.
Pinchaud, K., Maguin Gaté, K., Olivier, J.-L.
L’acide arachidonique alimentaire : un acteur à deux faces dans le cerveau et la maladie d’Alzheimer ? L’acide arachidonique est le second acide gras polyinsaturé cérébral et le premier de la série des ω-6. Les apports alimentaires d’acide arachidonique varient entre 50 et 300 mg/jour dans les régimes occidentaux mais pourraient être sous-estimés. Les triglycérides de la partie grasse des viandes fourniraient des quantités similaires aux phospholipides de la partie maigre. La maladie d’Alzheimer est une maladie neurodégénérative associée à l’âge et un problème de santé publique majeur dans le monde. Les oligomères de peptides β amyloïde en sont désormais reconnus comme l’agent principal, bien que la présence de la protéine tau est nécessaire à leur action. Avec d’autres auteurs, nous avons établi que la phospholipase A2 cytosolique, spécifique de l’acide arachidonique, assure les effets neurotoxiques des oligomères de peptide β amyloïde. Nous avons ensuite montré qu’un régime riche en acide arachidonique augmente la sensibilité des souris aux effets de ces oligomères, sans augmentation majeure de ses niveaux cérébraux. Ceci suggère que cet acide gras peut agir sur le cerveau par des effets périphériques comme une sub-inflammation dont le rôle dans la relation intestin-cerveau est discutée dans la littérature. Les apports alimentaires d’acide arachidonique devrait être intégrés dans la prévention de la maladie d’Alzheimer.
Arachidonic acid is the second polyunsaturated fatty acid in brain and the first one belonging to the ω-6 series. Dietary intakes of arachidonic are between 50 and 300 mg/day in western diets but they might be underestimated. Triglycerides from fat would provide similar amounts than phospholipids of lean meat. Alzheimer’s disease is an age-associated degenerative disease and a critical health concern worldwide. Amyloid-β peptide oligomers are presently recognized as the main and earliest agents of Alzheimer’s disease although their neurotoxicity requires the presence of tau protein. We and others established that the arachidonic-specific cytosolic phospholipase A2 is critical for the amyloid-β peptide oligomer neurotoxicity. Then, we showed that an arachidonic acid-rich diet increases the mouse sensitivity to the amyloid-β peptide oligomer deleterious effect without major increase of arachidonic acid levels in brain. This suggests that dietary arachidonic acid can exert its effects in brain through peripheral modifications. Involvement of systemic sub-inflammation and gut-brain communications are discussed based on the recent literature. The various data suggest that dietary arachidonic acid should be taken into account in the design of preventive strategies against Alzheimer’s disease.
Plos One, 17 (7), e0178668.
Guillot, X., Martin, H., Seguin-Py, S., Maguin-Gaté, K., Moretto, J., Totoson, P., Wendling, D., Demougeot, C., Tordi, N.
Objectives: Local cryotherapy is widely and empirically used in the adjuvant setting in rheumatoid arthritis treatment, however its own therapeutic and anti-inflammatory effects are poorly characterized. We aimed to evaluate the effects of local cryotherapy on local and systemic inflammation in Adjuvant-induced arthritis, a murine model of rheumatoid arthritis.
Methods: The effects of mild hypothermia (30°C for 2 hours) on cytokine protein levels (Multiplex/ELISA) were evaluated in vitro in cultured rat adjuvant-induced arthritis patellae. In vivo, local cryotherapy was applied twice a day for 14 days in arthritic rats (ice: n = 10, cold gas: n = 9, non-treated: n = 10). At day 24 after the induction of arthritis, cytokine expression levels were measured in grinded hind paws (Q-RT-PCR) and in the plasma (Multiplex/ELISA).
Results: In vitro, punctual mild hypothermia down-regulated IL-6 protein expression. In vivo, ice showed a better efficacy profile on the arthritis score and joint swelling and was better tolerated, while cold gas induced a biphasic response profile with initial, transient arthritis worsening. Local cryotherapy also exerted local and systemic anti-inflammatory effects, both at the gene and the protein levels: IL-6, IL-17A and IL-1β gene expression levels were significantly down-regulated in hind paws. Both techniques decreased plasma IL-17A while ice decreased plasma IL-6 protein levels. By contrast, we observed no effect on local/systemic TNF-α pathway.
Conclusions: We demonstrated for the first time that sub-chronically applied local cryotherapy (ice and cold gas) is an effective and well-tolerated treatment in adjuvant-induced arthritis. Furthermore, we provided novel insights into the cytokine pathways involved in Local cryotherapy's local and systemic anti-inflammatory effects, which were mainly IL-6/IL-17A-driven and TNF-α independent in this model.
Clinical and experimental immunology, 188 (2), pp. 208-218.
Verhoeven, F., Totoson, P., Maguin-Gaté, K., Prigent-Tessier, A., Marie, C., Wendling, D., Moretto, J., Prati, C., Demougeot, C.
To determine the effect of glucocorticoids (GCs) on endothelial dysfunction (ED) and on traditional cardiovascular (CV) risk factors in the adjuvant-induced arthritis (AIA) rat model. At the first signs of AIA, a high dose (HD) [10 mg/kg/day, intraperitoneally (i.p.), GC-HD] or low dose (LD) (1 mg/kg/day, i.p., GC-LD) of prednisolone was administered for 3 weeks. Endothelial function was studied in aortic rings relaxed with acetylcholine (Ach) with or without inhibitors of nitric oxide synthase (NOS), cyclooxygenase 2 (COX-2), arginase, endothelium derived hyperpolarizing factor (EDHF) and superoxide anions (?O–2°) production. Aortic expression of endothelial NOS (eNOS), Ser1177-phospho-eNOS, COX-2, arginase-2, p22phox and p47phox was evaluated by Western blotting analysis. Arthritis scores, blood pressure, heart rate and blood levels of cytokines, triglycerides, cholesterol and glucose were measured. GC-HD but not GC-LD reduced arthritis score significantly and improved Ach-induced relaxation (P < 0·05). The positive effect of GC-HD resulted from increased NOS activity and EDHF production and decreased COX-2/arginase activities and O–2° production. These functional effects relied upon increased phospho-eNOS expression and decreased COX-2, arginase-2 and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression. Despite the lack of effect of GC-LD on ED, it increased NOS and EDHF and down-regulated O–2° pathways but did not change arginase and COX-2 pathways. GC-HD increased triglycerides levels and blood pressure significantly (P < 0·05). Both doses of GCs decreased to the same extent as plasma interleukin (IL)-1β and tumour necrosis factor (TNF)-α levels (P < 0·05). Our data demonstrated that subchronic treatment with prednisolone improved endothelial function in AIA via pleiotropic effects on endothelial pathways. These effects occurred independently of the deleterious cardiometabolic effects and the impact of prednisolone on systemic inflammation.
Plos One, 11 (1), e0146744.
Totoson, P., Maguin-Gaté, K., Nappey, M., Wendling, D., Demougeot, C.
Objectives: To determine mechanisms involved in endothelial dysfunction (ED) during the course of arthritis and to investigate the link between cytokines, chemokines and osteoprotegerin.
Approach and results: Experiments were conducted on aortic rings at day 4 (preclinical), day 11 (onset of disease), day 33 (acute disease) and day 90 (chronic disease) after adjuvant-induced arthritis (AIA) in Lewis rats. At day 4, the unique vascular abnormality was a reduced norepinephrine-induced constriction. At day 11, endothelial function assessed by the relaxation to acetylcholine was normal despite increased cyclo-oxygenase-2 activity (COX-2) and overproduction of superoxide anions that was compensated by increased nitric oxide synthase (NOS) activity. At day 33, ED apparition coincides with the normalization of NOS activity. At day 90, ED was only observed in rats with a persisting imbalance between endothelial NOS and COX-2 pathways and higher plasma levels of IL-1β and TNFα. Plasma levels of IL-1β, TNFα and MIP-1α negatively correlated with Ach-induced relaxation throughout the course of AIA.
Conclusions: Our data identified increased endothelial NOS activity as an important compensatory response that opposes the ED in the early arthritis. Thereafter, a cross-talk between endothelial COX-2/NOS pathways appears as an important element for the occurrence of ED. Our results encourage determining the clinical value of IL-1β, TNFα and MIP-1α as biomarkers of ED in RA.
Rheumatology (Oxford), 55 (7), pp. 1308-1317.
Totoson, P., Maguin-Gaté, K., Prigent-tessier, A., Monnier, A., Verhoeven, F., Marie, C., Wendling, D., Demougeot, C.
Objectives: To determine the effect of etanercept on endothelial dysfunction and on traditional cardiovascular (CV) risk factors in the adjuvant-induced arthritis (AIA) rat model.
Methods: At the first signs of arthritis, etanercept (10 mg/kg/3 days, s.c.) or saline was administered for 3 weeks in AIA rats. Body weights and arthritis scores were monitored daily. Endothelial function was studied in aortic rings relaxed with acetylcholine (Ach) with or without inhibitors of nitric oxide synthase (NOS), cyclo-oxygenase (COX-2), arginase, endothelium-derived hyperpolarizing factor and superoxide anions (O2 (-)°) production. Aortic expression of endothelial nitic oxide synthase (eNOS), Ser1177-phospho-eNOS, COX-2, arginase-2, p22(phox) and p47(phox) was evaluated by western blotting analysis. Blood pressure, heart rate and blood levels of triglycerides, cholesterol and glucose were measured.
Results: Etanercept significantly reduced arthritis score (P < 0.001). It improved Ach-induced relaxation (P < 0.05) as a result of increased NOS activity, decreased COX-2/arginase activities and decreased O2 (-)° production. These functional effects relied on increased eNOS expression and phosphorylation, and decreased COX-2, arginase-2 and p22(phox) expressions. No correlation was found between arthritis score and Ach-induced relaxation. The treatment did not change triglycerides, cholesterol and glucose levels, but significantly increased systolic blood pressure and heart rate (P < 0.05).
Conclusion: Our data demonstrated that efficient dosage of etanercept on inflammatory symptoms improved endothelial function in AIA. This beneficial effect on endothelial function is disconnected from its impact on CV risk factors and relates to pleiotropic effects of etanercept on endothelial pathways. These results suggest that etanercept could be a good choice for patients with rheumatoid arthritis at high risk of CV events.
Arthritis research and therapy, 18 (1), pp. 258.
Verhoeven, F., Prati, C., Maguin-Gaté, K., Wendling, D., Demougeot, C.
Rheumatoid arthritis (RA) is the most common systemic autoimmune disease characterized by articular and extra-articular manifestations involving cardiovascular (CV) diseases. RA increases the CV mortality by up to 50 % compared with the global population and CV disease is the leading cause of death in patients with RA. There is growing evidence that RA favors accelerated atherogenesis secondary to endothelial dysfunction (ED) that occurs early in the course of the disease. ED is a functional and reversible alteration of endothelial cells, leading to a shift of the actions of the endothelium towards reduced vasodilation, proinflammatory state, proliferative and prothrombotic properties. The mechanistic links between RA and ED have not been fully explained, but growing evidence suggests a role for traditional CV factors, auto-antibodies, genetic factors, oxidative stress, inflammation and iatrogenic interventions such as glucocorticoids (GCs) use. GCs have been used in RA for several decades. Whilst their deleterious CV side effects were described in the 1950s, their effect on CV risk associated with inflammatory arthritis remains subject for debate. GC might induce negative effects on endothelial function, via a direct effect on endothelium or via increasing CV risk factors. Conversely, they might actually improve endothelial function by decreasing systemic and/or vascular inflammation. The present review summarizes the available data on the impact of GCs on endothelial function, both in normal and inflammatory conditions, with a special focus on RA patients.
Colloque annuel de la Société Cerveau et Maladies Cérébrovasculaires 2021, 28 mai, Dématérialisé
Morel, C., Maguin Gaté, K., Christophe, A., Jubreaux, J., Paoli, J., Degiorgio, C., Bouillaud-Kremarik, P., Grova, N., Schroeder, H.
Introduction: Evidence is now growing that exposure to environmental pollutants during the critical period of early-life brain development may be a strong risk factor, contributing to the emergence of neurobehavioral disorders later in life. The present study aims at evaluating the developmental neurotoxicity of an early exposure to an environmental chemical of high concern for human health, hexabromocyclododecane (HBCDD), a persistent organobromine flame retardant, in comparison with VPA, a common anti-epileptic drug known to induce developmental disorders including teratogenicity and neurobehavioral disturbances. HBCDD is a brominated flame retardant added to foam materials as a technical mixture of 3 isomers with the α-one to be of most concern for human health. Nowadays, little is known about the neurotoxicity of this isomer. A previous study (Maurice et al., Toxicol. Teratol., 2015) highlighted that a daily exposure of rat pups to α-HBCDD during gestation and lactation (66 ng/kg/day) induced early disturbances in locomotor maturation, exploratory activity and level of anxiety later in life.
Material et Methods: In order to assess neurobehavioral impairments induced by a perinatal exposure to HBCDD or VPA in the F1 generation at different postnatal ages from PND1 to PND122, pregnant Wistar rats were divided into three groups: Control, VPA, and HBCDD. HBCDD-exposed rats were administered daily p.o. during gestation and lactation (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. Anxiety and social behavior were assessed at two time points (juvenile PND 41 and adult age PND 122) by using the elevated-plus-maze and the social recognition test.
Results: The present results point out the ability of both compounds to induce subtle behavioral disturbances that may be quite different between the two chemicals.
Conclusion: The results of the social recognition test associated with the measurements of the cytochrome oxydase activity and epigenetic changes 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.
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.
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.
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.
43ème Colloque de la Société de Neuroendocrinologie, 2-4 octobre, Tours, France
Pinchaud, K., Hafeez, Z., Chatel, J.-M., Chadi, S., Auger, S., Dary, A., Maguin Gaté, K., Olivier, J.-L.
L’acide arachidonique (ARA) est le second acide gras polyinsaturé dans le cerveau. L’apport d’ARA est associé à la consommation d’aliments d’origine animale qui semble sous-estimée dans les régimes occidentaux. Une précédente étude de notre laboratoire a montré qu’un régime enrichi en ARA à hauteur de 1% augmente la sensibilité des souris BalB/C males à la neurotoxicité des oligomères de peptides β-amyloïdes, considérés comme étant un des principaux acteurs de la maladie d’Alzheimer. L’objectif de cette étude est d’évaluer l’impact d’un régime enrichi en ARA sur les fonctions cérébrales au travers de modifications du microbiote intestinal et d’altération des communications intestin-cerveau. Pour cela, deux groupes de souris BalB/C ont été nourries avec un régime moyennement hyperlipidique HL-ARA (15% de lipides non enrichi en ARA) ou HL+ARA (15% de lipides et enrichi en ARA à hauteur de 1%) ou encore Std-ARA 5% de lipides non enrichi en ARA) durant 8 semaines complètes. Notre étude n’a montré aucune différence significative concernant le poids des animaux durant l’expérimentation dans chacun des groupes, excepté une augmentation du poids du tissu adipeux mésentérique pour le groupe HL-ARA. Une augmentation du groupe de Bifidobacteriaceae (anti-inflammatoires) dans le microbiote intestinal des souris nourries avec le régime HL-ARA a été mise en évidence comparé au groupe Std-ARA. Cette augmentation de Bifidobacteriaceae est corrélée avec une plus forte présence de lipides dans le régime mais cet effet est renversé par l’ajout d’ARA dans le régime. Aucune modification des marqueurs de l’inflammation n’a été détecté dans le plasma et les fèces de chacun des groupes de souris, mais une augmentation du marqueur des astrocytes GFAP a été observée dans l’hippocampe des souris nourries avec le régime HL+ARA. Il serait intéressant d’étudier les altérations de communication entre l’intestin et cerveau incluant les signaux neuroendocriniens afin de comprendre la cascade impliquée dans la modulation des fonctions cérébrales par l’intestin.
Arachidonic acid (ARA) is the second polyunsaturated fatty acid in the brain. ARA intake is associated with consumption of animal origin products and seems to be underestimated in western diet. A previous study in our laboratory showed that a diet containing 1% ARA increased the sensitivity of male Balb/C mice to the neurotoxicity of the amyloid-β peptide oligomers, considered as the main Alzheimer’s disease agents. The objective of this study was to evaluate the impact of dietary ARA intake on brain functions through gut microbiota modifications and alteration of gut-brain communications. For this, two groups of male BalB/C mice were orally fed with moderately high fat diet, i.e., HL-ARA (15% lipid without ARA) and HL+ARA (15% lipid with 1% ARA) and the third group was fed on standard diet (Std-ARA, 5% lipids without ARA) during 9 weeks. No significant difference was observed in weight gain among the 3 groups except an increase in mesenteric fat tissue in HL-ARA diet group. An increase in Bifidobacteriaceae group (potentially anti-inflammatory) in gut microbiota of HL-ARA diet group was noted compared to standard diet group. This increase in Bifidobacteriaceae was correlated to high lipid contents in diet but this effect was reversed in HL+ARA diet group. No modifications in inflammatory markers were highlighted in plasma and feces samples of the three groups. Contrariwise, higher expression levels of the Glial fibrillary acidic protein were observed in hippocampus of HL+ARA group. It could be interesting to further investigate alterations of the gut-brain communications including neuroendocrine signals.