Sensibilité au glucose du cerveau chez le rat (implication de l'hypothalamus, détermination des acteurs cellulaires et moléculaires)

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

Dexamethasone inhibits the maturation of newly formed neurons and glia supplemented with polyunsaturated fatty acids

International audienceStress bears a negative impact on adult neurogenesis. High levels of corticoids have been shown to inhibit neural stem cell proliferation, and are considered responsible for the loss of neural precursors. Their effects on the differentiation of the glial and neuronal lineages have been less studied. We examined the effect of dexamethasone (Dex), a synthetic glucocorticoid, on the differentiation of rat neural stem cells in vitro. Dex had no effect on the differentiation of cells cultured under standard conditions. Since we previously determined that NSC, when cultured under classical conditions, were deprived of polyunsaturated fatty acids (PUFA), and displayed phospholipid compositions very different from the in vivo figures [1], we examined the effect of Dex under PUFA supplementation. Dex impaired neuron and oligodendrocyte maturation in PUFA-supplemented cells, demonstrated by the reduction of neurite lengths and oligodendrocyte sizes. This effect was mediated by the glucocorticoid receptor (GR), since it was eliminated by mifepristone, a GR antagonist, and could be relayed by a reduction of ERK phosphorylation. We determined that GR was associated with PPAR 13 and a under basal conditions, and that this association was disrupted when PUFA were added in combination with Dex. We assumed that this effect on the receptor status enabled the effect of Dex on PUFA supplemented cells, since we determined that the binding to the glucocorticoid response element was higher in cells incubated with PUFA and Dex. In conclusion, corticoids can impair NSC differentiation, and consequently impact the entire process of neurogenesis

Expression and localization of adiponectin receptors in rat hypothalamus

National audienc

Récepteurs AdipoR1 et R2 à l'adiponectine dans les cellules neuronales : mise en évidence et signalisation associée

National audienc

Rôle du dialogue entre le tissu adipeux et l’intestin dans le maintien de l’homéostasie intestinale

National audienc

Short‐term intermittent hypoxia induces simultaneous systemic insulin resistance and higher cardiac contractility in lean mice

International audienceBackground: Intermittent hypoxia (IH) is the major feature of obstructive sleep apnea syndrome, well-known to induce cardiometabolic complications. We previously demonstrated that IH induces hyperinsulinemia and associated altered insulin signaling in adipose tissue, liver, and skeletal muscle, but impact of IH on cardiac insulin signaling and functional/structural consequences remains unknown. Therefore, the aims of this study were to investigate in both lean and obese mice the effects of chronic IH on the following: (1) cardiac insulin signaling and (2) cardiac remodeling and function. Methods: C57BL/6 J male mice were fed low-fat (LFD) or high-fat (HFD) diet for 20 weeks, and exposed to IH (21-5% FiO2, 60 s cycle, 8 h/day) or normoxia (N) for the last 6 weeks. Systemic insulin sensitivity was evaluated by an insulin tolerance test. Cardiac remodeling and contractile function were assessed by cardiac ultrasonography. Ultimately, hearts were withdrawn for biochemical and histological analysis. Results: In LFD mice, IH-induced hyperinsulinemia and systemic insulin resistance that were associated with increased phosphorylations of cardiac insulin receptor and Akt on Tyr1150 and Ser473 residues, respectively. In addition, IH significantly increased cardiac interstitial fibrosis and cardiac contractility. In the HFD group, IH did not exert any additional effect, nor on insulin/Akt signaling, nor on cardiac remodeling and function. Conclusion: Our study suggests that, despite systemic insulin resistance, IH exposure mediates an adaptive cardiac response in lean but not in obese mice. Further studies are needed to investigate which specific mechanisms are involved and to determine the long-term evolution of cardiac responses to IH

The age-related hippocampal alterations of glutamatergic neurotransmission are aggravated by ω3 PUFA deficiency and reduced by fish oil supplementation in rats

International audienc

Intermittent Hypoxia Triggers Early Cardiac Remodeling and Contractile Dysfunction in the Time‐Course of Ischemic Cardiomyopathy in Rats

International audienceBACKGROUND Sleep‐disordered breathing is associated with a poor prognosis (mortality) in patients with ischemic cardiomyopathy. The understanding of mechanisms linking intermittent hypoxia (IH), the key feature of sleep‐disordered breathing, to ischemic cardiomyopathy progression is crucial for identifying specific actionable therapeutic targets. The aims of the present study were (1) to evaluate the impact of IH on the time course evolution of cardiac remodeling and contractile dysfunction in a rat model of ischemic cardiomyopathy; and (2) to determine the impact of IH on sympathetic activity, hypoxia inducible factor‐1 activation, and endoplasmic reticulum stress in the time course of ischemic cardiomyopathy progression. METHODS AND RESULTS Ischemic cardiomyopathy was induced by a permanent ligature of the left coronary artery in male Wistar rats (rats with myocardial infarction). Rats with myocardial infarction were then exposed to either IH or normoxia for up to 12 weeks. Cardiac remodeling and function were analyzed by Sirius red and wheat germ agglutinin staining, ultrasonography, and cardiac catheterization. Sympathetic activity was evaluated by spectral analysis of blood pressure variability. Hypoxia‐inducible factor‐1α activation and burden of endoplasmic reticulum stress were characterized by Western blots. Long‐term IH exposure precipitated cardiac remodeling (hypertrophy and interstitial fibrosis) and contractile dysfunction during the time course evolution of ischemic cardiomyopathy in rodents. Among associated mechanisms, we identified the early occurrence and persistence of sympathetic activation, associated with sustained hypoxia‐inducible factor‐1α expression and a delayed pro‐apoptotic endoplasmic reticulum stress. CONCLUSIONS Our data provide the demonstration of the deleterious impact of IH on post–myocardial infarction remodeling and contractile dysfunction. Further studies are needed to evaluate whether targeting sympathetic nervous system or HIF‐1 overactivities could limit these effects and improve management of coexisting ischemic cardiomyopathy and sleep‐disordered breathing

Chronic dietary exposure to a glyphosate-based herbicide results in total or partial reversibility of plasma oxidative stress, cecal microbiota abundance and short-chain fatty acid composition in broiler hens

International audienceGlyphosate-based herbicides (GBHs) are massively used in agriculture. However, few studies have investigated the effects of glyphosate-based herbicides on avian species although they are largely exposed via their food. Here, we investigated the potential reversibility of the effects of chronic dietary exposure to glyphosate-based herbicides in broiler hens. For 42 days, we exposed 32-week-old hens to glyphosate-based herbicides via their food (47 mg/kg/day glyphosate equivalent, glyphosate-based herbicides, n = 75) corresponding to half glyphosate’s no-observed-adverse-effect-level in birds. We compared their performance to that of 75 control animals (CT). Both groups (glyphosate-based herbicides and control animals) were then fed for 28 additional days without glyphosate-based herbicides exposure (Ex-glyphosate-based herbicides and Ex-control animals). Glyphosate-based herbicides temporarily increased the plasma glyphosate and AMPA (aminomethylphosphonic acid) concentrations. Glyphosate and aminomethylphosphonic acid mostly accumulated in the liver and to a lesser extent in the leg muscle and abdominal adipose tissue. Glyphosate-based herbicides also temporarily increased the gizzard weight and plasma oxidative stress monitored by TBARS (thiobarbituric acid reactive substances). Glyphosate-based herbicides temporarily decreased the cecal concentrations of propionate, isobutyrate and propionate but acetate and valerate were durably reduced. The cecal microbiome was also durably affected since glyphosate-based herbicides inhibited Barnesiella and favored Alloprevotella . Body weight, fattening, food intake and feeding behavior as well as plasma lipid and uric acid were unaffected by glyphosate-based herbicides. Taken together, our results show possible disturbances of the cecal microbiota associated with plasma oxidative stress and accumulation of glyphosate in metabolic tissues in response to dietary glyphosate-based herbicides exposure in broiler hens. Luckily, glyphosate-based herbicides at this concentration does not hamper growth and most of the effects on the phenotypes are reversible

Genome, Environment, Microbiome and Metabolome in Autism (GEMMA) Study Design: Biomarkers Identification for Precision Treatment and Primary Prevention of Autism Spectrum Disorders by an Integrated Multi-Omics Systems Biology Approach

Autism Spectrum Disorder (ASD) affects approximately 1 child in 54, with a 35-fold increase since 1960. Selected studies suggest that part of the recent increase in prevalence is likely attributable to an improved awareness and recognition, and changes in clinical practice or service availability. However, this is not sufficient to explain this epidemiological phenomenon. Research points to a possible link between ASD and intestinal microbiota because many children with ASD display gastro-intestinal problems. Current large-scale datasets of ASD are limited in their ability to provide mechanistic insight into ASD because they are predominantly cross-sectional studies that do not allow evaluation of perspective associations between early life microbiota composition/function and later ASD diagnoses. Here we describe GEMMA (Genome, Environment, Microbiome and Metabolome in Autism), a prospective study supported by the European Commission, that follows at-risk infants from birth to identify potential biomarker predictors of ASD development followed by validation on large multi-omics datasets. The project includes clinical (observational and interventional trials) and pre-clinical studies in humanized murine models (fecal transfer from ASD probands) and in vitro colon models. This will support the progress of a microbiome-wide association study (of human participants) to identify prognostic microbiome signatures and metabolic pathways underlying mechanisms for ASD progression and severity and potential treatment response