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Objective : Obesity significantly elevates the odds of developing mood disorders. Chronic consumption of a saturated high-fat diet (HFD) elicits anxiodepressive behavior in a manner linked to metabolic dysfunction and neuroinflammation in mice. Dietary omega-3 polyunsaturated fatty acids (n-3 PUFA) can improve both metabolic and mood impairments by relieving inflammation. Despite these findings, the effects of n-3 PUFA supplementation on energy homeostasis, anxiodepressive behavior, brain lipid composition, and gliosis in the diet-induced obese state are unclear.Methods : Male C57Bl/6J mice were fed a saturated high-fat diet (HFD) or chow for 20 weeks. During the last 5 weeks mice received daily gavage (“supplementation”) of fish oil (FO) enriched with equal amounts of docosahexaenoic (DHA) and eicosapentaenoic acid (EPA) or control corn oil. Food intake and body weight were measured throughout while additional metabolic parameters and anxiety- and despair-like behavior (elevated-plus maze, light–dark box, and forced swim tasks) were evaluated during the final week of supplementation. Forebrain lipid composition and markers of microglia activation and astrogliosis were assessed by gas chromatography–mass spectrometry and real-time PCR, respectively.Results : Five weeks of FO supplementation corrected glucose intolerance and attenuated hyperphagia in HFD-induced obese mice without affecting adipose mass. FO supplementation also defended against the anxiogenic and depressive-like effects of HFD. Brain lipids, particularly anti-inflammatory PUFA, were diminished by HFD, whereas FO restored levels beyond control values. Gene expression markers of brain reactive gliosis were supressed by FO.Conclusions : Supplementing a saturated HFD with FO rich in EPA and DHA corrects glucose intolerance, inhibits food intake, suppresses anxiodepressive behaviors, enhances anti-inflammatory brain lipids, and dampens indices of brain gliosis in obese mice. Together, these findings support increasing dietary n-3 PUFA for the treatment of metabolic and mood disturbances associated with excess fat intake and obesity.

Despite the controversy regarding the existence and physiological relevance of class A G protein-coupled receptor dimerization, there is substantial evidence for functional interactions between the dopamine D2 receptor (D2R) and the adenosine A2A receptor (A2AR). A2AR-D2R complexes have been detected in rodent brains by proximity ligation assay; however, their existence in the human brain has not been demonstrated. In this study, we used Brightfield proximity ligation assay, combined with a systematic sampling and a parameter-free naive Bayesian classifier, and demonstrated proximity between the D2R and the A2AR in the adult human ventral striatum, consistent with their colocalization within complexes and the possible existence of D2R-A2AR heteromers. These methods are applicable to the relative quantification of proximity of two proteins, as well as the expression levels of individual proteins., METHOD SUMMARY Brightfield proximity ligation assay was used to assess the expression of G protein-coupled receptors and their proximity in postmortem adult human brains. A novel automated machine learning method (Bayesian optimized PLA signal sorting) was developed to automatically quantify Brightfield proximity ligation assay data.

International audience; Composite processing strongly affects the size of lignocellulosic fibers, and consequently the mechanical properties of the final product. Using a reliable method for the analysis of fiber length and diameter distributions is thus crucial for the understanding of fiber behavior during processing. In this study, three different techniques, X-ray microtomography, 2D scanning and automated fiber analyzer, were compared in terms of their reliability for the characterization of dimensions of two kinds of lignocellulosic fibers, hemp and miscanthus, in polymer-natural fiber composites. Statistical analysis was employed to interpret fiber size distributions. The study confirmed that interpreting the dimensions of natural fiber is still a difficult task. The inherent limitations of the measuring methods make each technique complementary to the others in terms of length scale. The choice of the technique is, therefore, strictly dependent on fiber dimensions and the aim of the work.

International audience; A high rate of patients with schizophrenia (SZ) does not sufficiently respond to antipsychotic medication, which is associated with relapses and poor outcomes. Chronic peripheral inflammation has been repeatedly associated with schizophrenia risk and particularly to poor responders to treatment as usual with cognitive impairment in SZ subjects. The objective of present study was to confirm if ultra resistance to treatment in schizophrenia (UTRS) was associated to chronic peripheral inflammation in a non-selected sample of community-dwelling outpatients with schizophrenia. Participants were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia and received a thorough clinical assessment, including recording of current treatment. Current psychotic symptomatology was evaluated by the Positive and Negative Syndrome scale for Schizophrenia (PANSS). UTRS was defined by current clozapine treatment + PANSS total score ≥ 70. Functioning was evaluated by the Global Assessment of Functioning scale. High sensitivity CRP (hs-CRP) was measured for each participant as a proxy to define peripheral low-grade inflammation. 609 stabilized community-dwelling SZ subjects (mean age = 32.5 years, 73.6% male gender) have been included. 60 (9.9%) patients were classified in the UTRS group. In multivariate analyses, UTRS has been associated independently with chronic peripheral inflammation (OR = 2.6 [1.2–5.7], p = 0.01), illness duration (0R = 1.1 [1.0–1.2], p = 0.02) and impaired functioning (OR = 0.9 [0.9–0.9], p = 0.0002) after adjustment for age, sex, current daily tobacco smoking, metabolic syndrome and antidepressant consumption. Peripheral low-grade inflammation is associated with UTRS. Future studies should explore if anti-inflammatory strategies are effective in UTRS with chronic low-grade peripheral inflammation.

International audience; Background and aims For a given genotype, the observed variability of tree forms results from the stochasticity of meristem functioning and from changing and heterogeneous environmental factors affecting biomass formation and allocation. In response to climate change, trees adapt their architecture by adjusting growth processes such as pre- and neoformation, as well as polycyclic growth. This is the case for the teak tree. The aim of this work was to adapt the plant model, GreenLab, in order to take into consideration both these processes using existing data on this tree species. Methods This work adopted GreenLab formalism based on source-sink relationships at organ level that drive biomass production and partitioning within the whole plant over time. The stochastic aspect of phytomer production can be modelled by a Bernoulli process. The teak model was designed, parameterized and analysed using the architectural data from 2- to 5-year-old teak trees in open field stands. Key results Growth and development parameters were identified, fitting the observed compound organic series with the theoretical series, using generalized least squares methods. Phytomer distributions of growth units and branching pattern varied depending on their axis category, i.e. their physiological age. These emerging properties were in accordance with the observed growth patterns and biomass allocation dynamics during a growing season marked by a short dry season. Conclusions Annual growth patterns observed on teak, including shoot pre- and neoformation and polycyclism, were reproduced by the new version of the GreenLab model. However, further updating is discussed in order to ensure better consideration of radial variation in basic specific gravity of wood. Such upgrading of the model will enable teak ideotypes to be defined for improving wood production in terms of both volume and quality.

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International audience; In occidental societies, high fat and high sugar diets often coincide with episodes of stress. The association is likely to modify brain energy control. Brain insulin signalling is rarely studied in stressed individuals consuming high fat diets. Furthermore the effects of cinnamon supplement are not known in these conditions. Therefore, we exposed rats, over a 12-week period, to a control (C) or a high fat/high fructose (HF/HFr) diet that induces peripheral insulin resistance. A cinnamon supplement (C+CN and HF/HFr +CN) was added or not. After diet exposure, one group of rats was exposed to a 30-min restraint followed by a 10-min open-field test, their combination featuring a moderate stressor, the other rats staying unstressed in their home cages. The insulin signalling in hippocampus and frontal cortex was studied through the mRNA expression of the following genes: insulin receptor (Ir), insulin receptor substrate (Irs1), glucose transporters (Glut1 and Glut3), glycogen synthase (Gys1) and their modulators, Akt1 and Pten. In C rats, stress enhanced the expression of Ir, Irs1, Glut1, Gys1 and Akt1 mRNA. In C+CN rats, stress induced an increase in Pten but a decrease in Gys1 mRNA expression. In HF/HFr rats, stress was associated with an increase in Pten mRNA expression. In HF/HFr+CN rats, stress increased Pten mRNA expression but also decreased Gys1 mRNA expression. This suggests that a single moderate stress favours energy refilling mechanisms, an effect blunted by a previous HF/HFr diet and cinnamon supplement.

International audience; The diagnosis of Type 1 Diabetes (T1D) in ever younger children led us to question the impact of insulin deficiency or chronic hyperglycemia on cerebral development and memory performances. Here, we sought abnormalities in these traits in a model of streptozotocin-induced diabetes in juvenile rats treated or not by insulin. We made the assumption that such alterations would be related, at least in part, to excessive glucocorticoid exposition in hippocampal neurons. We have compared 3 groups of juvenile rats: controls, untreated diabetics and insulin-treated diabetics. Diabetes was induced by streptozotocin (65 mg/kg IP/day, 2 consecutive days), at postnatal days 21 and 22 and a subcutaneous pellet delivering 2 U of insulin/day was implanted in treated diabetic rats 3 days later. Three weeks after diabetes induction, cognitive performances (Y maze, object location and recognition tests), in vivo brain structure (brain volume and water diffusion by structural magnetic resonance imaging), and hippocampal neurogenesis (immunohistochemical labeling) measurements were undertaken. Corticosterone levels were evaluated in plasma under basal and stress conditions, and within hippocampus together with 11β-dehydrocorticosterone to assess 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity. The comparison of the three experimental groups revealed that, compared to controls, untreated diabetic rats showed decreased cognitive performances in Y-maze and object location test (p

n-3 Long-chain PUFA (n-3 LC-PUFA), particularly EPA and DHA, play a key role in the maintenance of brain functions such as learning and memory that are impaired during ageing. Ageing is also associated with changes in the DHA content of brain membranes that could contribute to memory impairment. Limited studies have investigated the effects of ageing andn-3 LC-PUFA supplementation on both blood and brain fatty acid compositions. Therefore, we assessed the relationship between fatty acid contents in plasma and erythrocyte membranes and those in the hippocampus, striatum and cerebral cortex during ageing, and after a 5-month period of EPA/DHA supplementation in rats. In the blood, ageing was associated with an increase in plasma DHA content, whereas the DHA content remained stable in erythrocyte membranes. In the brain, ageing was associated with a decrease in DHA content, which was both region-specific and phospholipid class-specific. In EPA/DHA-supplemented aged rats, DHA contents were increased both in the blood and brain compared with the control rats. The present results demonstrated thatn-3 LC-PUFA level in the plasma was not an accurate biomarker of brain DHA status during ageing. Moreover, we highlighted a positive relationship between the DHA levels in erythrocyte phosphatidylethanolamine (PE) and those in the hippocampus and prefrontal cortex in EPA/DHA-supplemented aged rats. Within the framework of preventive dietary supplementation to delay brain ageing, these results suggest the possibility of using erythrocyte PE DHA content as a reliable biomarker of DHA status in specific brain regions.

International audience; With the aim to reveal common genomic regions influencing phenotypes related to HPA axis function and metabolism, we did a quantitative trait loci (QTL) study in a F2 population obtained from the cross-breeding between 2 contrasted rat strains, LOU/C and Fischer 344. QTL determining phenotypes related first to corticotropic function were searched: plasma corticosterone (Cort) in control and stress conditions, after a dexamethasone suppression treatment (glucocorticoid receptor related-effect), and mineralocorticoid receptor-mediated urinary response to aldosterone. Then, phenotypes related to metabolism were studied on the same animals: body composition, basal and post-insulin plasma glucose, plasma free fatty acids, leptin, and insulin. Finally, we analyzed the overlapping regions between these QTL and looked for candidate genes within these regions. The gene NR3C1 encoding the glucocorticoid receptor was confirmed to be central in the link between hypothalamic-pituitary-adrenal (HPA) axis function and fat deposition, and its metabolic consequences. Among the other candidate genes detected, most contain a glucocorticoid responsive element, strengthening our hypothesis of common genetic determinism between HPA axis and metabolism.

International audience; Current treatments of depression include psychological, pharmacological and physical approaches. Pharmacological interventions to treat depression have previously focused on modifying dysfunctional neurotransmitter systems. Overall, these treatments have demonstrated an ability to manage major depression but otucomes continue to be poor in many patients, especially those with long term illness or with previous multiple relapses. This may be due to the fact that depression is a systemic and neuroprogressive illness involving multiple biological pathways such as immunological factors. There is substantial evidence that cytokine therapies induce depressive symptoms in clinical populations. The model of cytokine-induced depression has provided important information relative to the risk factors and biological pathways involved in the etiology of depressive symptoms and, most importantly, the identification and knowledge of these factors has allowed new treatment targets to be explored. When an exogenous cytokine such as interferon-alpha is administered, proinflammatory cytokines are activated, leading to alterations in neurotransmission and endocrine pathways and producing neurotoxicity. Several new treatments for depression acting through pathways other than amine neurotransmission have emerged in recent years. The regulation of the inflammatory response, the decrease in the activity of the hypothalamic-pituitary-adrenal axis and the prevention of neurotoxicity are potential targets for new drugs. Though these drugs are mostly at the proof-of-concept stage, some of them have already shown promising results for the treatment of depression.

International audience; Residing at high altitude may lead to reduced blood oxygen saturation in the brain and altered metabolism in frontal cortical brain areas, probably due to chronic hypobaric hypoxia. These changes may underlie the increased rates of depression and suicidal behavior that have been associated with life at higher altitudes. To test the hypothesis that hypobaric hypoxia is responsible for development of mood disorders due to alterations in neurochemistry, we assessed depression-like behavior in parallel to levels of brain metabolites in rats housed at simulated altitude. 32 female Sprague Dawley rats were housed either in a hypobaric hypoxia chamber at 10,000 ft of simulated altitude for 1 week or at local conditions (4500 ft of elevation in Salt Lake City, Utah). Depression-like behavior was assessed using the forced swim test (FST) and levels of neurometabolites were estimated by in vivo proton magnetic resonance spectroscopy in the frontal cortex, the striatum and the hippocampus at baseline and after a week of exposure to hypobaric hypoxia. After hypoxia exposure the animals demonstrated increased immobility behavior and shortened latency to immobility in the FST. Elevated ratios of myo-inositol, glutamate, and the sum of myo-inositol and glycine to total creatine were observed in the frontal cortex of hypoxia treated rats. A decrease in the ratio of alanine to total creatine was also noted. This study shows that hypoxia induced alterations in frontal lobe brain metabolites, aggravated depression-like behavior and might be a factor in increased rates of psychiatric disorders observed in populations living at high altitudes.

International audience; OBJECTIVES: The development of the gastrointestinal tract depends on many elements, including glucocorticoids. In the current study, we evaluated the effects of early weaning on corticosterone function and the growth of rat gastric mucosa. METHODS: By using Wistar rats submitted to early weaning at 15 d, we analyzed plasma corticosterone, corticosteroid-binding globulin (CBG), and glucocorticoid receptor (GR) distribution in the gastric epithelium. RESULTS: With the use of radioimmunoassay, we found that early weaning increased corticosterone concentration at day 16 and 17 in test subjects as compared with controls, whereas it was equivalent between groups at day 18. CBG binding capacity decreased during treatment, and it was significantly lower at day 18. At this age, GR levels and distribution in the gastric mucosa were also reduced as compared with suckling counterparts. To reduce corticosterone activity during early weaning and to explore cell proliferation responses, we administered RU486 to 15-d-old pups. We found that cytoplasmic GR reached a peak after 48 h, whereas nuclear levels remained constant, thereby confirming the inhibition of receptor function. Next, by checking gastric proliferative responses, we observed that RU486 induced higher DNA synthesis and mitotic indices in test subjects as compared with control groups. CONCLUSIONS: We demonstrated that early weaning changed corticosterone activity by increasing hormone levels, reducing CBG binding capacity, and decreasing GR distribution in the gastric epithelium. These modifications seem to be important to the reorganization of gastric growth after the abrupt interruption of suckling.

International audience; The exact nature and pathophysiology of fatigue remain largely elusive despite its high prevalence in physically ill patients. Studies on the relationship between the immune system and the central nervous system provide a new perspective on the mechanisms of fatigue. Inflammatory mediators that are released by activated innate immune cells at the periphery and in the central nervous system alter the metabolism and activity of neurotransmitters, generate neurotoxic compounds, decrease neurotrophic factors, and profoundly disturb the neuronal environment. The resulting alterations in fronto-striatal networks together with the activation of insula by inflammatory interoceptive stimuli underlie the many dimensions of fatigue including reduced incentive motivation, decreased behavioral flexibility, uncertainty about usefulness of actions, and awareness of fatigue.

Chantier qualité GA; International audience; Objective: Since a reduction of the insulin/IGF-1 signaling cascade extends life span in many species and IGF-1 signaling might partly mediate the effects of caloric restriction (CR), an experimental intervention for increasing longevity, the purpose of the present study was to use quantitative trait loci (QTL) analysis, an unbiased genetic approach, to identify particular regions of the genome influencing plasma IGF-1 levels in an F2 intercross between F344 and LOU/C rats; the latter being an inbred strain of Wistar origin, considered as a model of healthy aging since it resists to age (and diet)-induced obesity. Design: F1 hybrids were obtained by crossbreeding LOU/C with F344 rats, and then F1 were bred inter se to obtain the F2 population, of which 93 males and 94 females were studied. Total plasma IGF-1 levels were determined by radioimmunoassay. A genome scan of the F2 population was made with 100 microsatellite markers) selected for their polymorphism between LOU/C and F344 strains (and by covering evenly the whole genome. Results: By simple interval mapping sex-dependent QTLs were found on chromosome 17 in males and on chromosome 18 in females. By multiple interval mapping, additional QTLs were found on chromosomes 1, 4, 5, 6, 12, 15 and 19 in males and on chromosomes 3, 5, 6, 12 and 17 in females. Only the markers D1Rat196 and D12Mgh5 were found in both males and females. The majority of QTLs corresponded to metabolic syndrome (cardiac function: n = 45 (30%), obesity/diabetes: n = 22 (15%), inflammation: n = 19 (13%) and only a limited number to body weight: n = 13 (9%), proliferation (n = 10 (7%) or ossification: n = 7 (5%). Ninety-six candidate genes were located on the different QTLs. A significant proportion of these genes are connected to IGF-1 production and receptor pathways (n = 18) or metabolic syndrome (n = 11). Conclusions: Subsequent studies are necessary to determine whether the genetic networks underscored are also involved in age-associated obesity, diabetes and inflammation as well as cardiovascular impairments.

International audience; Sleep disruption is prevalent in patients and survivors of breast cancer. Most patients undergoing chemotherapy will experience transient sleep disruption, and nearly 60% will have chronic sleep problems. Numerous factors contribute to sleep disruption in women diagnosed with breast cancer. Sleep disruption is a consequence of several biological alterations, including circadian disruption and immune and metabolic deregulations. These systems also play significant roles in the control and progression of breast cancer. Sleep disruption is associated with many side effects and psychiatric and medical comorbidities. This article discusses the relationship between stress and posttraumatic stress disorder, depression and fatigue, and how sleep disturbance might be the cause or consequence of these disorders. Current evidence for management of sleep disturbance in breast cancer and high chronic use of hypnotic medication in this population is also discussed. Finally, the differences in management of sleep disturbance during acute cancer care and during the survivorship phase are discussed. More research is needed on accurate and timely assessment of sleep disturbance associated with breast cancer, and additional tailored approaches for the management of sleep problems in breast cancer should be developed.

International audience; Within the central nervous system (CNS) the traditional role of microglia has been in brain infection and disease, phagocytosing debris and secreting factors to modify disease progression. This led to the concept of “resting” versus “activated” microglia. However, this is misleading because multiple phenotypic and morphological stages of microglia can influence neuronal structure and function in any condition and recent evidence extends their role to healthy brain homeostasis. The present work was thus aimed at reappraising the concept of morphofunctional activity of microglia in a context of peripheral acute immune challenge, where microglial activity is known to be modified, using the new state-of-the-art techniques available. To do so, mice were injected peripherally with lipopolysaccharide, a potent inducer of cerebral inflammation, and we assessed early cytokines production, phenotype, motility and morphology of microglial cells. Our results showed that LPS induced a widespread inflammatory response both peripherally and centrally, as revealed by the quantification of cytokines levels. We also found an alteration of microglial motility that was confirmed by in vivo studies showing an overall reduction of microglial processes length in the hippocampus of LPS-treated animals. Finally, analysis of various surface receptors expression revealed that LPS did not significantly impact microglial phenotype 2 h after the injection but rather induced an increase of CD11b+/CD45high cells. These latter may be at the vasculature, at the CNS vicinity, or may have invaded the CNS.

International audience; Background/aims: To determine whether the 17-hydroxyprogesterone (17-OHP)/cortisol ratio as a marker of immature11-beta hydroxylase activity can predict severe systemic hypotension in preterm neonates. Methods: Serum cortisol and 17-OHP concentrations were measured in capillary blood deposited on blotter paper on day 3 post-natal age (Day 3) in infants less than 32 weeks postmenstrual age (PMA). The predictive value of 17-OHP/cortisol ratio for a first episode of systemic hypotension occurring after Day 3 (FESH) was evaluated. Results: Of 105 infants included, 14 patients (13%) presented a FESH. Neither the 17-OHP/cortisol ratio, nor the 17-OHP or cortisol concentrations were associated with the occurrence of a FESH when adjusted for potential confounding factors. 17-OHP and cortisol were inversely associated to PMA (r = ﹣0.36 and ﹣0.40, respectively). Cortisol, but not 17-OHP, was associated with the type of hospitalization unit, the respiratory support and the presence of a patent ductus arteriosus. The 17-OHP/cortisol ratio was associated with the type of hospitalization unit only. Conclusions: The 17-OHP/ cortisol ratio at Day 3 did not predict the occurrence of a first episode of systemic hypotension after Day3 inpreterm neonates.

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Fatigue is frequent in patients with diabetes and this symptom appears to be more prominent in type 2 rather than type 1 diabetic subjects. Chronic inflammation represents one characteristic of type 2 diabetes that may contribute to fatigue symptoms. This possibility was assessed in a sample of 20 type 2 diabetic patients relatively to a group of 20 type 1 diabetic subjects. Specific dimensions of fatigue, including general fatigue, physical fatigue, reduced activity, mental fatigue and reduced motivation, were assessed using the Multidimensional-Fatigue-Inventory (MFI). Biological assays comprised the measurement of serum inflammatory markers [high-sensitive C-reactive-protein (hsCRP), high-sensitive interleukin-6 (hsIL-6), high-sensitive tumor-necrosis-factor-alpha (hsTNF-alpha) and neopterin]. Clinical parameters including indexes of adiposity were collected. In comparison to type 1 diabetic subjects, patients with type 2 diabetes exhibited higher fatigue scores, notably in the dimensions of general fatigue, physical fatigue and reduced activity, together with greater levels of inflammatory markers that correlated with indexes of adiposity. Regression analyses controlling for diabetes duration, insulin treatment status, glycemic control and fasting status, indicated that levels of inflammatory markers, in particular hsIL-6, hsCRP and neopterin, were associated with MFI fatigue dimensions in type 2 diabetic patients. Mediation analyses revealed that adiposity did not significantly account for the relationship of inflammatory markers with fatigue scores albeit coefficient regressions decreased somewhat when this variable was controlled for in regression models. These findings indicate that systemic low-grade inflammation relates to fatigue symptoms in patients with type 2 diabetes and suggest the involvement of inflammatory processes in the pathophysiology of diabetes-related fatigue.

National audience; Neurobehavioral symptoms are frequently reported in patients with diabetes. Nevertheless, the characterization of the specific symptom dimensions that develop in diabetic patients with respect to disease phenotype and treatment status remains obscure. This study comparatively assessed fatigue symptoms and cognitive performance using a dimensional approach in 21 patients with insulin-treated type 1 diabetes, 24 type 2 diabetic patients either insulin-free or undergoing insulin treatment for at least six months, and 15 healthy subjects. Specific dimensions of fatigue were assessed using the Multidimensional-Fatigue-Inventory (ME!). Cognitive performance on tests of choice reaction time, pattern recognition memory and spatial planning was evaluated using the Cambridge-Neuropsychological-Automated-Battery (CANTAB). Body mass index (BMI) and glycated-hemoglobin (HbA1C) concentrations were collected, as well as information on diabetes complications and disease duration. Patients with type 2 diabetes, regardless of insulin treatment status, exhibited higher scores of fatigue, primarily in the dimensions of general and physical fatigue as well as reduced activity. Cognitive alterations, in the form of longer reaction times and impaired spatial planning, were also detected in type 2 diabetic patients treated with insulin. These alterations were overall unrelated to glucose control, as reflected in HbA1C levels, and were not explained by complications and duration of diabetes. No specific alteration was measured in type 1 diabetic patients who exhibited fatigue scores and cognitive performance comparable to healthy participants. While associated with fatigue, increased BMI did not significantly account for the relationship of type 2 diabetes with general fatigue and physical fatigue. BMI, however, modulated the association of type 2 diabetes with reduced activity and the association of insulin-treated type 2 diabetes with psychomotor slowing. These findings reveal specific fatigue and cognitive symptoms in patients with type 2 diabetes and suggest the involvement of differential pathophysiological processes.

International audience; Lack of compensatory or even reduced food intake is frequently observed in weight-losing cancer patients and contributes to increased morbidity and mortality. Our previous work has shown increased transcription factor expression in the hypothalamus and ventral striatum of anorectic rats bearing small tumors. mRNA expression of molecules known to be involved in pathways regulating appetite in these structures was therefore assessed in this study. Given that pain, pro-inflammatory cytokines and metabolic hormones can modify food intake, spinal cord cellular activation patterns and plasma concentrations of cytokines and hormones were also studied. Morris hepatoma 7777 cells injected subcutaneously in Buffalo rats provoked a 10% lower body weight and 15% reduction in food intake compared to free-feeding tumor-free animals 4weeks later when the tumor represented 1-2% of body mass. No differences in spinal cord activation patterns or plasma concentration of pro-inflammatory cytokines were observed between groups. However, the changes in plasma ghrelin and leptin concentrations found in food-restricted weight-matched rats in comparison to ad libitum-fed animals did not occur in anorectic tumor-bearing animals. Real-time PCR showed that tumor-bearing rats did not display the increase in hypothalamic agouti-related peptide mRNA observed in food-restricted weight-matched animals. In addition, microarray analysis and real-time PCR revealed increased ventral striatal prostaglandin D synthase expression in food-restricted animals compared to anorectic tumor-bearing rats. These findings indicate that blunted hypothalamic AgRP mRNA expression, probably as a consequence of relatively high leptin and low ghrelin concentrations, and reduced ventral striatal prostaglandin D synthesis play a role in maintaining cancer-associated anorexia.

Chantier qualité GA; International audience; We aimed to distinguish mineralocorticoid (MR) from glucocorticoid receptor (GR) actions in the nutritional differences between the Fischer 344 (F344) and LOU/C (LOU) rat strains. The decrease of urinary Na+/K+ ratio induced via MR activation by aldosterone and decrease of circulating lymphocyte counts exerted via GR activation by dexamethasone revealed a higher efficiency of corticosteroid receptor in LOU than in F344 rats. Afterward, we submitted F344 and LOU male rats to adrenalectomy and to substitution treatments with agonists of MR or GR under 3 successive diets—standard, free choice between chow and pork lard, and an imposed high-fat/high-sugar diet—to explore the involvement of the interactions between activation of corticosteroid receptors and diet on food intake, body composition, and metabolic blood parameters in these rats. Lastly, we measured energy expenditure and substrate oxidization in various experimental conditions in LOU and F344 rats by indirect calorimetry. In LOU rats, we showed greater basal and MR-induced energy expenditure, diet-induced thermogenesis, and lipid oxidization. We showed that the F344 rat strain constitutes a relevant model of the unfavorable effects exerted by glucocorticoids via GR on food preference for high-calorie diets, abdominal fat deposition, diabetes, and other deleterious consequences of visceral obesity. Contrary to F344 rats, the LOU rats did not exhibit the expected visceral fat deposition linked to GR activation. This strain is therefore a relevant model of resistance to diet-induced obesity and to the deleterious effects exerted by glucocorticoids on metabolism.

International audience; To date, convergent data on the role of retinoic acid in the mature brain have established that this molecule, which acts as a hormone, helps to preserve cerebral plasticity by controlling dendritic spine density as well as hippocampal neurogenesis. Deterioration in cerebral plasticity seems to be at the base of the cognitive decline disease. Furthermore, the transcription of several genes, known as muted, in Alzheimer’s patients and whose transcripts are involved in the formation of senile plaques, are controlled by retinoic acid. As seen in other nutrients, aging leads to a lower production of retinoic acid; a phenomenon probably accentuated by the fact that Western populations consume an insufficient amount of vitamin A (60% of the population has a consumption lower than the recommendations). These two phenomena (i.e. level of consumption, the lack of activation of vitamin A) accompanied by important individual differences, would help to explain why some patients have an almost normal aging process, whereas others gradually develop cognitive disorders and then, the disease. A better understanding of the role of a collapse of the retinoid status in the genesis of Alzheimer lesions could, beyond the definition of a preventive nutritional strategy, open therapeutic perspectives, through the use of molecules targeting the nuclear receptors.; La vitamine A est une vitamine liposoluble qui présente des rôles importants dans différents tissus de l’organisme. Elle est impliquée dans la vision, dans le maintien de l’intégrité des surfaces épithéliales, dans l’immunité, la reproduction ou encore dans la croissance et le développement (Blomhoff et Blomhoff, 2006). En dehors de son rôle dans la vision, la vitamine A agit principalement par l’intermédiaire de son métabolite l’acide rétinoïque (AR) qui, en se liant à des récepteurs nucléaires, régule l’expression de gènes dans les tissus cibles.Il est bien connu que les rétinoïdes, et en particulier l’AR, jouent un rôle capital dans le développement du système nerveux central, mais ce n’est que récemment que son action dans le cerveau adulte a retenu l’attention des scientifiques. Les données actuellement disponibles sur ce sujet suggèrent qu’une régulation très fine de l’expression des gènes cibles de l’AR est fondamentale pour des fonctions cérébrales optimales, telles que la plasticité synaptique, l’apprentissage et la mémoire. Plus récemment encore, des données provenant de plusieurs études mettent en évidence l’implication de la voie de signalisation des rétinoïdes dans l’étiologie de la maladie d’Alzheimer (MA).

BACKGROUND: Structure–activity relationships are often reported in scientific studies. These may be employed in searching for new acceptable biocides to use against harmful microorganisms, because the biocides used hitherto encounter various problems, including lack of efficiency, high toxicity and persistence. Nowadays, scientists are trying to find new, environmentally acceptable biocides to replace these earlier biocides. Different compounds from renewable materials have been studied and have shown pronounced antifungal activity against wood fungi. These include aminopolysaccharide derivatives and different quaternary ammonium polymers. A biological study carried out with these products indicated a possible relationship between amino groups and differences in biological activity observed. RESULTS: In this study, an amino group was successively fixed to different carbon atoms of glucose, and glucosamine was also modified by both N-alkylation and quaternisation. The impact of the amino group position on antifungal activity against two wood decay fungi was investigated. The amino group at the anomeric position showed the highest antifungal activity against both Coriolus versicolor Quel. and Poria placenta (Fr.) Cooke. Furthermore, the positive impact of both N-alkylation and quaternisation on the growth of both strains was demonstrated. CONCLUSION: The anomeric position of the amino group and the N-alkylation and quaternisation of amino sugars considerably increase the antifungal activity of these compounds. Copyright © 2010 Society of Chemical Industry

International audience; In the framework of the Silent Wall ANR project, the CMM and the US2B are associated in order to characterize and to model fibrous media studying 3D images acquired with an X-Ray microtomograph used by the US2B. The device can make 3D images of maximal size 2304 3 voxels with resolutions in the range of 2-15 μm. Using mathematical morphology, measurements on the 3D X-Ray CT images are performed to characterize materials. For example, measuring the covariance on these images of an acoustic insulating material made of wooden fibers highlights the transverse isotropy of the fibers orientations in the xOy planes perpendicular to the compression Oz axis. Moreover, it is possible to extract other morphological properties, such as the size distribution either of the fibers or of the pores by estimating the morphological opening granulometry of the considered medium. Finally the morphological tortuosity of the fibrous and porous networks are estimated from geodesic propagations. The tortuosity is a parameter which can help to link physical, acoustic, and morphological properties of the material. Moreover the effects of the boundary layer, where viscous and thermal damping of the sound take place, are studied from the point of view of the tortuosity.

During extrusion of starchy products, the molten material is forced through a die so that the sudden pressure drop causes part of the water to vaporize, giving an expanded cellular structure. The moisture is lost due to evaporation and heat transfer, as the material cools down. Thus, the material crosses glass transition Tg and becomes solid. No simple deterministic model is available to describe satisfactory dynamic, multiphysic and multiphase phenomena during expansion. Current models are too complex to be coupled with simple mechanistic model of co-rotating twin-screw extrusion process, in order to predict the cellular structure of starchy foams.Our objective is to elaborate a phenomenological model of expansion, simple enough to be coupled with Ludovic, a simulation software of twin screw extrusion process. From experimental results that cover a wide range of thermomechanical conditions, a concept map of influence relationships between input and output variables is built. It takes into account the phenomena of bubbles nucleation, growth, coalescence, shrinkage and setting, in a viscoelastic medium. The input variables are the moisture content MC, melt temperature Tp, specific mechanical energy SME, shear viscosity η; at the die exit, computed by Ludovic®, and the melt storage modulus E’(Tp>g). The latter represents the elongational viscosity, and takes into account the influence of starch amylose content. The outputs of the model are the macrostructure (expansion indices and anisotropy factor), and cellular structure (fineness) of solid foams, determined by X-ray tomography. Then a general model is suggested: VEI = α (η/η0)^n in which VEI is the volumetric expansion index. The model parameters, α and n depend on Tp, MC, SME and E’. The link between macroscopic anisotropy and fineness is also established, allowing the prediction of cellular structure. Finally, the model is validated using experimental data of wheat flour extrusion from literature.

This paper deals with metallo-phthalocyanines and functionalized nanocarbons as sensitive materials for microsensors development dedicated to BTX monitoring at room temperature. Because of the nature of gas/materials interactions involved, QCM has been chosen as transducer. Sensors were tested in different concentration ranges. Out of different phthalocyanines materials studied, tert-butyl substituted metallo-phthalocyanines showed highest sensitivity. Aiming to further improve the sensitivity, ttb-CuPc/CNT hybrid nanomaterials were synthesized. The sensitivity measured for this hybrid nanomaterial was found to be greater as compared to individual sensitivity of ttb-CuPc and CNT.

A finite element model was developed to study the influence of aerial architecture on the structural dynamics of trees. The model combines a complete description of the axes of the aerial architecture of the plant with numerical techniques suitable for dynamic nonlinear analyses. Trees were modeled on the basis of morphological measurements that were previously made on three 4-year-old Pinus pinaster Ait. saplings originating from even-aged stands. Calculated and measured oscillations were compared to evaluate model behavior. The computations allowed the characteristics of the fundamental mode of vibration to be estimated with satisfactory accuracy. Inclusion of a topological description of the aerial system in a mechanical model provided insight into the effect of tree architecture on tree dynamic behavior. Simplifications of the branching pattern in the model led to overestimations of the natural swaying frequency of saplings by 10 to 20%. Inadequate values of stem and root anchorage stiffness resulted in errors of 10 to 20%. Modeling results indicated that aerodynamic drag of needles is responsible for 80% of the damping in the studied trees. Additionally, damping of stem movement is reduced by one half when branch oscillations are not considered. It appears that the efficiency of the dissipative mechanisms depends directly on crown topology.

Lux06b; International audience; A general method combining the volume averaging technique and image analysis is proposed to determine the effective thermal conductivity tensor of real fibrous materials featuring local anisotropic thermal properties. The application of mathematical morphology tools on 3D images of wood based fibrous insulators allows a thorough investigation of the microstructure of these materials. A representative elementary volume is determined and the geometrical structure and local anisotropy are studied and quantified. The classical closure problem coming from the one equation model is solved on the 3D thermal conductivity tensor field and the effective thermal conductivity is computed. Good agreement with available experimental data is achieved.

The perinatal period is a critical period during which the quality of the environment has long lasting effects on adult phenotype. Early adversity in childhood has been associated with higher risks to develop neuropsychiatric disorders later in life. Nowadays, modern societies are characterized by a high consumption of fat. Although these changes also affect nutritional environment during development, the impact on brain functioning and behavior remains unknown. The aim of my thesis was to examine the programming effects of maternal high-fat diet (HFD, western diet) and early stress on offspring phenotype. In the first part, we showed that maternal HFD leads to metabolic disturbances in adult offspring and sensitized to memory deficits if the HFD is maintained throughout life. In the second part, we explored the effects of the combination between maternal HFD and chronic maternal separation (3h/day, postnatal day 2 to 14). Maternal separation enhances motivation for palatable food and combined with maternal HFD exacerbates vulnerability to diet-induced obesity. In contrast, maternal HFD protects the offspring against the emotional and cognitive impairments induced by maternal separation. This protective effect of maternal HFD could be related to the increase of maternal care in stressed dams exposed to HFD and to the attenuation of neurodevelopmental alterations in the prefrontal cortex of stressed pups. In conclusion, my work demonstrates that stress and nutrition during early life interact and influence later adult phenotype.; La période périnatale est une période critique lors de laquelle la qualité de l’environnement influence durablement le phénotype. Ainsi, l’adversité dans l’enfance affecte la santé mentale à l’âge adulte. Nos habitudes alimentaires se sont modifiées avec une augmentation de la consommation d’aliments gras. Ces changements altèrent l’environnement nutritionnel précoce, mais l’effet à long terme sur le cerveau est mal connu. L’objectif de ma thèse était d’examiner, grâce un modèle animal, l’impact d’un régime maternel hyperlipidique (HL) modélisant le régime des sociétés occidentales et d’un stress de séparation maternelle sur la programmation du phénotype de la descendance adulte. Dans une 1ière étude, nous avons montré que le régime maternel HL entraine des modifications métaboliques chez la descendance et vulnérabilise à l’émergence de déficits mnésiques si l’exposition au régime est maintenue. Dans une 2ème étude, nous avons exploré les effets combinés du régime maternel HL et d’un stress de séparation maternelle (3h/jour, postnatal jours 2 à 14). Le stress précoce augmente la motivation pour des aliments palatables et combiné au régime maternel HL exacerbe la prise de poids sous régime palatable. En revanche, le régime maternel HL protège la descendance des perturbations émotionnelles et mnésiques associées au stress précoce. Cet effet pourrait être sous-tendu par l’augmentation du comportement maternel sous régime HL et par l’atténuation des altérations développementales du cortex préfrontal des ratons stressés. En conclusion, mon travail démontre que la nutrition et le stress interagissent en période périnatale et modifient à long terme le phénotype.

International audience; L’alimentation maternelle au cours de la période périnatale joue un rôle essentiel dans la croissance et le développement cérébral des descendants. L’incorporation adéquate d’acide docosahexaénoique (DHA) dans le cerveau est un véritable challenge en nutrition périnatale car le DHA pourrait limiter les processus neuroinflammatoires et atténuer les déficits cognitifs observés à l’âge adulte. L’objectif de l’étude est d’évaluer l’effet de régimes maternels différant par la qualité des lipides, le ratio n-6/n-3 et par l’apport en DHA sur l’incorporation de DHA dans le cortex préfrontal des petits 14 jours après la naissance (P14) et à l’âge adulte (P90).

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International audience; The brain is highly enriched with fatty acids. These include the polyunsaturated fatty acids (PUFAs) arachidonic acid and docosahexaenoic acid, which are largely esterified to the phospholipid cell membrane. Once PUFAs are released from the membrane, they can participate in signal transduction, either directly or after enzymatic conversion to a variety of bioactive derivatives ('mediators'). PUFAs and their mediators regulate several processes within the brain, such as neurotransmission, cell survival and neuroinflammation, and thereby mood and cognition. PUFA levels and the signalling pathways that they regulate are altered in various neurological disorders, including Alzheimer's disease and major depression. Diet and drugs targeting PUFAs may lead to novel therapeutic approaches for the prevention and treatment of brain disorders.

International audience; Understanding how malnutrition contributes to depression is building momentum. In the present study we unravel molecular and cellular mechanisms by which nutritional disturbances lead to impaired emotional behaviour in mice. Here we report that nutritional n-3 polyunsaturated fatty acids (PUFA) deficiency induces a chronic stress state reflected by disrupted glucocorticoid receptor (GR)-mediated signalling pathway along with hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. This hyperactivity in turn resulted in neuronal atrophy in the dorsolateral (dl)- and dorsomedial (dm)- prefrontal cortex (PFC) and subsequent mood-related behaviour alterations, similarly to chronic social defeat stress. Supplementation of n-3 PUFA prevented detrimental chronic social defeat stress-induced emotional and neuronal impairments by impeding HPA axis hyperactivity. These results indicate a role for dietary n-3 PUFA in the prevention of HPA axis dysfunction associated with the development of some neuropsychiatric disorders including depression.

International audience; Low dietary intake of the n-3 polyunsaturated fatty acids (PUFAs) is a causative factor of neurodevelopmental disorders. However the mechanisms linking n-3 PUFAs low dietary intake and neurodevelopmental disorders are poorly understood. Microglia, known mainly for their immune function in the injured or infected brain, have recently been demonstrated to play a pivotal role in regulating maturation of neuronal circuits during normal brain development. Disruption of this role during the perinatal period therefore could significantly contribute to psychopathologies with a neurodevelopmental neurodevelopmental component. N-3 PUFAs, essential lipids and key structural components of neuronal membrane phospholipids, are highly incorporated in cell membranes during the gestation and lactation phase. We previously showed that in a context of perinatal n-3 PUFAs deficiency, accretion of these latter is decreased and this is correlated to an alteration of endotoxin-induced inflammatory response. We thus postulated that dietary n-3 PUFAs imbalance alters the activity of microglia in the developing brain, leading to abnormal formation of neuronal networks. We first confirmed that mice fed with a n-3 PUFAs deficient diet displayed decreased n-3 PUFAs levels in the brain at post-natal days (PND)0 and PND21. We then demonstrated that n-3 PUFAs deficiency altered microglia phenotype and motility in the post-natal developing brain. This was paralleled by an increase in pro-inflammatory cytokines expression at PND21 and to modification of neuronal plasticity-related genes expression. Overall, our findings show for the first time that a dietary n-3 PUFAs deficiency from the first day of gestation leads to the development of a pro-inflammatory condition in the central nervous system that may contribute to neurodevelopmental alterations.

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International audience; Neuropsychiatric symptoms are frequent in obesity. In addition to their substantial economic and health impact, these symptoms significantly interfere with the quality of life and social function of obese individuals. While the pathophysiological mechanisms underlying obesity-related neuropsychiatric symptoms are still under investigation and remain to be clearly identified, there is increasing evidence for a role of inflammatory processes. Obesity is characterized by a chronic low-grade inflammatory state that is likely to influence neuropsychiatric status given the well-known and highly documented effects of inflammation on brain activity/function and behavior. This hypothesis is supported by recent findings emanating from clinical investigations in obese subjects and from experimentations conducted in animal models of obesity. These studies converge to show that obesity-related inflammatory processes, originating either from the adipose tissue or gut microbiota environment, spread to the brain where they lead to substantial changes in neurocircuitry, neuroendocrine activity, neurotransmitter metabolism and activity, and neurogenesis. Together, these alterations contribute to shape the propitious bases for the development of obesity-related neuropsychiatric comorbidities.