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Microglia are the immune effector cells of the central nervous system (CNS) and react to pathologic events with a complex process including the release of nitric oxide (NO). NO is a free radical, which is toxic for all cells at high concentrations. To target an exaggerated NO release, we tested a library of 16 544 chemical compounds for their effect on lipopolysaccharide (LPS)-induced NO release in cell line and primary neonatal microglia. We identified a compound (C1) which significantly reduced NO release in a dose-dependent manner, with a low IC50 (252 nM) and no toxic side effects in vitro or in vivo. Target finding strategies such as in silico modelling and mass spectroscopy hint towards a direct interaction between C1 and the nitric oxide synthase making C1 a great candidate for specific intra-cellular interaction with the NO producing machinery.

The inhibitory GABAergic system in the brain is involved in the etiology of various psychiatric problems, including autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), and others. These disorders are influenced not only by genetic but also by environmental factors, such as preterm birth, although the mechanisms underlying are not known. In a translational hyperoxia model, exposing mice pups at age P5 to 80% oxygen for 48 hours to mimic a steep rise of oxygen exposure caused by preterm birth from in utero into room air, we documented a persistent reduction of cortical mature parvalbumin expressing interneurons until adulthood. Developmental delay of cortical myelin was observed together with decreased expression of oligodendroglial glial cell-derived neurotrophic factor (GDNF), a factor being involved in interneuronal development. Electrophysiological and morphological properties of remaining interneurons were unaffected. Behavioral deficits were observed for social interaction, learning, and attention. These results elucidate that neonatal oxidative stress can lead to decreased interneuron density and to psychiatric symptoms. The obtained cortical myelin deficit and decreased oligodendroglial GDNF expression indicate an impaired oligodendroglial-interneuronal interplay contributes to interneuronal damage.

Sport relies on the coordination of teammates’ behaviours to maximise performance. This responsibility is often tasked to the captain, coach, or manager of the team. Such individuals might therefore ask, “How can I influence my team to perform better?” This chapter reviews literature that helps to answer that question by proposing that one mechanism leading to coordinated social performance is emotions. Ten years ago, van Kleef introduced the emotions as social information (EASI) theory to help explain how emotions regulate social interactions. This theory stipulates that emotional expressions influence others’ behaviour through affective and inferential processes. The nature of the influence depends on others’ motivation and ability to process the emotional expressions as well as on the perceived appropriateness of the expressions. Many theoretical and empirical articles that elucidate the mechanisms and moderating factors involved in such emotional influence have since been published. However, these have mostly been contextualised within social and organisational settings, such as personal relationships, group decision making, negotiation, customer service, and leadership. Given that sports settings are inherently emotional, we contend that emotional influence also occurs in sports. To support this point, we summarise the main tenets of EASI theory, apply them to the sports context, and review emerging findings on the social effects of emotional expressions in sports.

Ce rapport présente l'analyse des systèmes d'information économique agricole pour quatre filières aux USA : le blé et les pommes de terre dans l'état de Washington, les porcs dans l'Iowa et les tomates fraîches en Californie. Il comprend les résultats de l'enquête (numéro 211), leur analyse statistique et une synthèse. L'accent est mis sur la division du travail dans la production et la diffusion des services d'aide à la décision économique.

Summary: Sex differences in brain structure and function are of substantial scientific interest because of sex-related susceptibility to psychiatric and neurological disorders. Neuroinflammation is a common denominator of many of these diseases, and thus microglia, as the brain’s immunocompetent cells, have come into focus in sex-specific studies. Here, we show differences in the structure, function, and transcriptomic and proteomic profiles in microglia freshly isolated from male and female mouse brains. We show that male microglia are more frequent in specific brain areas, have a higher antigen-presenting capacity, and appear to have a higher potential to respond to stimuli such as ATP, reflected in higher baseline outward and inward currents and higher protein expression of purinergic receptors. Altogether, we provide a comprehensive resource to generate and validate hypotheses regarding brain sex differences. : Guneykaya et al. provide transcriptomic, proteomic, and functional data from male and female microglia, providing a resource for further investigation of sex-based differences in microglia. Keywords: microglia, sex differences, transcriptomics, proteomics

Maternal immune activation (MIA) during pregnancy has been linked to an increased risk of developing psychiatric pathologies in later life. This link may be bridged by a defective microglial phenotype in the offspring induced by MIA, as microglia have key roles in the development and maintenance of neuronal signaling in the central nervous system. The beneficial effects of the immunomodulatory treatment with minocycline on schizophrenic patients are consistent with this hypothesis. Using the MIA mouse model, we found an altered microglial transcriptome and phagocytic function in the adult offspring accompanied by behavioral abnormalities. The changes in microglial phagocytosis on a functional and transcriptional level were similar to those observed in a mouse model of Alzheimer's disease hinting to a related microglial phenotype in neurodegenerative and psychiatric disorders. Minocycline treatment of adult MIA offspring reverted completely the transcriptional, functional and behavioral deficits, highlighting the potential benefits of therapeutic targeting of microglia in psychiatric disorders.

The neurodevelopmental hypothesis of schizophrenia posits that schizophrenia is a psychopathological condition resulting from aberrations in neurodevelopmental processes caused by a combination of environmental and genetic factors which proceed long before the onset of clinical symptoms. Many studies discuss an immunological component in the onset and progression of schizophrenia. We here review studies utilizing animal models of schizophrenia with manipulations of genetic, pharmacologic, and immunological origin. We focus on the immunological component to bridge the studies in terms of evaluation and treatment options of negative, positive, and cognitive symptoms. Throughout the review we link certain aspects of each model to the situation in human schizophrenic patients. In conclusion we suggest a combination of existing models to better represent the human situation. Moreover, we emphasize that animal models represent defined single or multiple symptoms or hallmarks of a given disease.

OBJECTIVE: Glioma, such as anaplastic astrocytoma and glioblastoma multiforme, belong to the most aggressive neoplasms in humans. Microglia and peripheral macrophages are attracted towards glioma and their abundance positively correlates with malignancy, invasiveness and tumor grade. Gliomaexhibit an immunosuppressive milieu, and glioma-associated microglia/ macrophages are polarized towards an M2-like anti- inflammatory phenotype and actively support tumor growth, e.g. via the release of immune-suppressive cytokines, and factors that stimulate angiogenesis and tumor invasion. Here we seek to identify new glioma-regulated genes to further elucidate the pathways of glioma-microglia interaction. METHODS:In order to achieve this,wecompared the gene expression profiles of glioma-associated microglia/macrophages isolated from experimental allogeneic GL261 tumors and human gliomas with microglia and peritoneal macrophages isolated from control animals and humans. RESULTS: The microarray experiment we performed with RNA samples from CD11b+ MACS-sorted cells from GL261 tumors and naïve brains revealed highly altered gene expression patterns in tumor-associated microglia/macrophages. More than 600 genes were more than 5-fold up- or downregulated in tumor-associated cells when compared to control cells. The qPCRvalidation we performed with FACS-sorted samples confirmed the regulation of our target genes and revealed that genes are either strongly upregulated in tumour-associated microglia or macrophages, but not in both cell types at the same time. This demonstrates that intrinsic microglia and invading macrophages fulfill different tasks in the tumor. We are currently collecting samples fromtheRCAStumor model to validate the expression of our target genes in an independent mouse tumor model. CONCLUSIONS: In future experiments we will confirm the expression of our target genes on protein level, using FACS, IHC and western blot. Furthermore we will test the expression of our target genes in RNA samples we are currently collecting from CD11b+ MACS sorted cells from human glioblastoma and normal brain samples.

Recently, neurotransmitters/neurohormones have been identified as factors controlling the function of microglia, the immune competent cells of the central nervous system. In this study, we compared the responsiveness of microglia to neurotransmitters/neurohormones. We freshly isolated microglia from healthy adult C57Bl/6 mice and found that only a small fraction (1-20%) responded to the application of endothelin, histamine, substance P, serotonin, galanin, somatostatin, angiotensin II, vasopressin, neurotensin, dopamine, or nicotine. In cultured microglia from neonatal and adult mice, a similarly small population of cells responded to these neurotransmitters/neurohormones. To induce a proinflammatory phenotype, we applied lipopolysaccaride (LPS) or interferon-gamma (IFN-{gamma}) to the cultures for 24 h. Several of the responding populations increased; however, there was no uniform pattern when comparing adult with neonatal microglia or LPS with IFN-{gamma} treatment. IL-4 as an anti-inflammatory substance increased the histamine-, substance P-, and somatostatin-sensitive populations only in microglia from adult, but not in neonatal cells. We also found that the expression of different receptors was not strongly correlated, indicating that there are many different populations of microglia with a distinct set of receptors. Our results demonstrate that microglial cells are a heterogeneous population with respect to their sensitivity to neurotransmitters/neurohormones and that they are more responsive in defined activation states.

Diffusion du document : INRA Unité d'Economie et Sociologie rurales CRA Auzeville BP 27 31326 Castanet-Tolosan (FRA); Cette analyse des données provenant d'une enquête conduite aux USA par les auteurs porte sur la production et la circulation des informations économiques agricoles. Les sources d'information (aide à la décision) d'acteurs variés sont empiriquement analysées. Les résultats montrent que les agences publiques occupent un important rôle de leader tant dans la production que dans la livraison finale de l'information. Les rôles d'une série d'intermédiaires qui ajoutent de la valeur à l'information publiquement disponible dans l'intérêt des décideurs sont aussi définis et analysés.

Ce chapitre développe et teste l'hypothèse que la tendance contemporaine à la marchandisation des services de vulgarisation agricole couplée avec le développement de technologies de conservation des ressources sophistiquées et coûteuses, contribue à une mauvaise allocation spatiale des ressources. Dans leur ensemble, les agriculteurs qui occupent la partie la moins vulnérable des campagnes ont accès à l'information et aux outils pour conserver et protéger le sol et les ressources en eau, tandis que les agriculteurs dans les régions de production les plus marginales et les plus fragiles écologiquement disposent d'un appui moins important.

Cet article montre l'importance de la participation des normes publiques et des acteurs publics dans le processus de production de connaissance et le développement économique. Les auteurs avancent que la tendance vers la science privée, particulièrement la recherche des universités américaines s'alliant avec des intérêts commerciaux, ont des implications négatives quant aux objectifs sociaux, dont l'innovation radicale, la compétitivité et l'équité sociale.