Molecular Imaging of Microglial Activation in Amyotrophic Lateral Sclerosis

There is growing evidence of activated microglia and inflammatory processes in the cerebral cortex in amyotrophic lateral sclerosis (ALS). Activated microglia is characterized by increased expression of the 18 kDa translocator protein (TSPO) in the brain and may be a useful biomarker of inflammation. In this study, we evaluated neuroinflammation in ALS patients using a radioligand of TSPO, 18F-DPA-714. Ten patients with probable or definite ALS (all right-handed, without dementia, and untreated by riluzole or other medication that might bias the binding on the TSPO), were enrolled prospectively and eight healthy controls matched for age underwent a PET study. Comparison of the distribution volume ratios between both groups were performed using a Mann-Whitney’s test. Significant increase of distribution of volume ratios values corresponding to microglial activation was found in the ALS sample in primary motor, supplementary motor and temporal cortex (p = 0.009, p = 0.001 and p = 0.004, respectively). These results suggested that the cortical uptake of 18F-DPA-714 was increased in ALS patients during the ‘‘time of diagnosis’’ phase of the disease. This finding might improve our understanding of the pathophysiology of ALS and might be a surrogate marker of efficacy of treatment on microglial activation

Plasma cortisol and faecal cortisol metabolites concentrations in stereotypic and non-stereotypic horses:do stereotypic horses cope better with poor environmental conditions?

BACKGROUND: Stereotypic behaviours, i.e. repetitive behaviours induced by frustration, repeated attempts to cope and/or brain dysfunction, are intriguing as they occur in a variety of domestic and captive species without any clear adaptive function. Among the different hypotheses, the coping hypothesis predicts that stereotypic behaviours provide a way for animals in unfavourable environmental conditions to adjust. As such, they are expected to have a lower physiological stress level (glucocorticoids) than non-stereotypic animals. Attempts to link stereotypic behaviours with glucocorticoids however have yielded contradictory results. Here we investigated correlates of oral and motor stereotypic behaviours and glucocorticoid levels in two large samples of domestic horses (N(Study1) = 55, N(Study2) = 58), kept in sub-optimal conditions (e.g. confinement, social isolation), and already known to experience poor welfare states. Each horse was observed in its box using focal sampling (study 1) and instantaneous scan sampling (study 2). Plasma samples (collected in study 1) but also non-invasive faecal samples (collected in both studies) were retrieved in order to assess cortisol levels. RESULTS: Results showed that 1) plasma cortisol and faecal cortisol metabolites concentrations did not differ between horses displaying stereotypic behaviours and non-stereotypic horses and 2) both oral and motor stereotypic behaviour levels did not predict plasma cortisol or faecal cortisol metabolites concentrations. CONCLUSIONS: Cortisol measures, collected in two large samples of horses using both plasma sampling as well as faecal sampling (the latter method minimizing bias due to a non-invasive sampling procedure), therefore do not indicate that stereotypic horses cope better, at least in terms of adrenocortical activity

PGC-1-Related Coactivator Modulates Mitochondrial-Nuclear Crosstalk through Endogenous Nitric Oxide in a Cellular Model of Oncocytic Thyroid Tumours

BACKGROUND:The PGC-1 related coactivator (PRC), which shares structural and functional features with PGC-1alpha, is believed to regulate several metabolic pathways as well as mitochondrial biogenesis. Its involvement in the early programming of cell proliferation suggests the existence of finely regulated crosstalk between mitochondrial functions and the cell cycle status. METHODOLOGY/PRINCIPAL FINDINGS:PRC-regulated pathways were explored in a cell-line model derived from mitochondrial-rich tumours with an essentially oxidative metabolism and specifically high PRC expression. The functional status of mitochondria was compared to the results of microarray analysis under conditions of temporal PRC inhibition. To specify the fine PRC regulation, the expression levels of the genes and proteins involved in the oxidative phosphorylation process were studied by real time quantitative PCR and western blotting. As in earlier studies on PGC-1alpha, we investigated the role of nitric oxide in PRC-regulated mitochondrial biogenesis and determined its action in the control of the phosphorylation status of the mitogen-activated protein kinase pathway. CONCLUSION/SIGNIFICANCE:We found that nitric oxide rapidly influences PRC expression at the transcriptional level. Focusing on mitochondrial energetic metabolism, we observed that PRC differentially controls respiratory chain complexes and coupling efficiency in a time-dependent manner to maintain mitochondrial homeostasis. Our results highlight the key role of PRC in the rapid modulation of metabolic functions in response to the status of the cell cycle

Termite sensitivity to temperature affects global wood decay rates.

Deadwood is a large global carbon store with its store size partially determined by biotic decay. Microbial wood decay rates are known to respond to changing temperature and precipitation. Termites are also important decomposers in the tropics but are less well studied. An understanding of their climate sensitivities is needed to estimate climate change effects on wood carbon pools. Using data from 133 sites spanning six continents, we found that termite wood discovery and consumption were highly sensitive to temperature (with decay increasing >6.8 times per 10°C increase in temperature)-even more so than microbes. Termite decay effects were greatest in tropical seasonal forests, tropical savannas, and subtropical deserts. With tropicalization (i.e., warming shifts to tropical climates), termite wood decay will likely increase as termites access more of Earth's surface

Etude du système dopaminergique par tomographie par émission monophotonique (apport dans le diagnostic précoce des maladies parkinsoniennes)

TOURS-BU Médecine (372612103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

L'intérêt de la TEP-FDG dans les carcinomes épidermodoïdes des voies aerodigestives supérieures

Les cancers ORL représentent le quatrième cancer le plus fréquent et la huitième cause de mortalité par cancer dans le monde. Il s'agit donc d'un réel problème de Santé Publique. Une prise en charge précoce et un bilan d'extension adapté sont primordiaux pour le pronostic et l'adaptation du traitement à l'extension tumorale et à l'état général du patient. La classification de l'extension tumorale repose sur la taille de la tumeur primitive et de l'envahissement ganglionnaire et métastasique. Elle est effectuée actuellement par un examen clinique, une panendoscopie, un bilan d'imagerie par tomodensitométrie (TDM) avec injonction de produit de contraste et manoeuvre de Valsalva, parfois imagerie par résonance magnétique. Certains auteurs ont montré une grande précision de la tomographie par émission de positions (TEP) avec 18F-fluoro-2-déoxy-glucose (FDG) pour le diagnostic de tumeur primitive et de ses métastases ganglionnaires et à distance. De plus, l'équipement des centres français en caméras hybrides TEP-TDM a apporté une aide importante pour la classification TNM des tumeurs ORL, permettant de distinguer une lésion maligne des fixations physiologiques. Notre étude a pour but de montrer l'intérêt de la TEP-TDM avec le 18F-FDG pour le bilan d'extension initiale de 49 carcinomes épidermoïdes ORL, dont 25 ont eu une classification histologique après exérèse tumorale et curage ganglionnaire. Nous avons montré que la TEP-TDM avec le 18F-FDG sous-estimait dans 20% des cas la taille de la tumeur, essentiellement lié à l'effet de volume partiel des petits tumeurs T1. Par contre, la TEP-TDM FDG a une très bonne valeur diagnostique pour l'extension ganglionnaire et le diagnostic des métastases à distance, remettant ainsi en cause le planning d'organisation des examens complémentaires à prévoir dans le bilan initial des tumeurs ORL. Il nous semble par contre nécessaire de prouver histologiquement toutes lésions hypermétaboliques découvertes si non attendues. Enfin notre étude a démontré la nécessité de définir une méthode consensuelle et reproductible pour le contourage tumoral afin d'améliorer la sensibilité de la classification T mais également dans le but d'aider au planning de contourage tumoral de la radiothérapie.TOURS-BU Médecine (372612103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Etude du système dopaminergique par tomographie par émission monophotonique (des modèles animaux à l'homme)

TOURS-BU Médecine (372612103) / SudocSudocFranceF

Influence of castration and immunization against GnRH on inflammatory response in pigs: preliminary results.

Surgical castration of male pigs at neonatal age is criticized for welfare reasons. Alternative solutions such as rearing entire males or immunocastrated animals exist, but it is necessary to evaluate their consequences on health. Indeed, given that sex hormones modulate immune function, castration and immunocastration might affect the immune development of pigs. The present study aimed at comparing for their inflammatory response entire pigs, neonatally surgically castrated pigs, pigs immunized against GnRH at 80 and 111 days (=immunocastration), and neonatally surgically castrated pigs immunized against GnRH. The immune (cytokine and blood formula), endocrine (cortisol) and metabolic (plasma glucose, lactate, free fatty acid and urea) responses to an LPS injection (O55:B5, 15µg/kg) at 147 days were investigated in blood samples collected through a jugular catheter from -30 to +1440 min post injection. Data from the two first replicates (5-6 animals per group) among three are presented. Neonatal surgical castration did not affect the IL-1b, IL-6 and TNF-α responses but accentuated the increase in cortisol (from 60 to 300 min) and, seemed to reduce the hypoglycaemia (240 - 300 min) after LPS. Immunization against GnRH seemed to lower the increase in lactate (90 min) and in free fatty acids (240 - 1440 min) after LPS. This attenuation might result directly from the lack of GnRH or from alterations due to the previous immune activation by vaccination

Effets de la castration et de l’immunocastration sur l’axe corticotrope et le système immunitaire des porcs

National audienceLa castration chirurgicale des porcs est controversée pour des raisons de bien‐être animal. Il est donc nécessaire d’étudier les alternatives potentielles comme la production de mâles entiers ou immunocastrés, et de vérifier que ces alternatives ne soulèvent pas de nouveaux problèmes de santé ou de bien‐être animal. Cette étude a été réalisée afin de comprendre les effets des hormones testiculaires sur l’immunité et la réactivité au stress des porcs. Elle se déroule sur 65 animaux répartis en 4 groupes expérimentaux : entiers, castrés chirurgicalement (à 5/6 jours d’âge), vaccinés contre la GnRH (immunocastrés), et castrés puis immunocastrés. Des prises de sang à 3, 4 et 5 mois permettent de valider l’effet des traitements sur les niveaux circulants de stéroïdes sexuels et d’étudier les populations lymphocytaires. Le cortisol est dosé dans la salive pour mesurer l’activité de l’axe corticotrope et la réactivité au stress. Les animaux sont abattus à 5 mois pour déterminer le développement des testicules, des surrénales et du thymus. Les résultats montrent que l’immunocastration induit une augmentation des concentrations salivaires de cortisol 24 jours après la première injection. La castration chirurgicale semble aussi accroître l’activité surrénalienne. La castration chirurgicale inhiberait partiellement le fonctionnement thymique des porcs (poids du thymus réduit à 5 mois,diminution du nombre de lymphocytes totaux et altération des pourcentages des différentes sous‐populations lymphocytaires sanguines à 4 mois et thymiques au stade d’abattage) alors que les effets de l’immunocastration sont moins clairs. Les conséquences potentielles de ces modifications sur la santé globale des animaux restent à déterminer

Exploration of early social behaviors and social styles in relation to individual characteristics in suckling piglets

International audienceSocial behavior is a key component of pig welfare on farms, but little is known on the development of social behaviors in piglets. This study aimed to explore social behaviors and identify early social styles in suckling piglets. Social behaviors of 68 piglets from 12 litters were scored continuously for 8 h per day at 21 and 42 days of age, and were included in a Hierarchical Clustering on Principal Components analysis to identify clusters of pigs with similar social styles. Social nosing represented 78% of all social interactions given. Three social styles were identified: low-solicited inactive animals (inactive), active animals (active), and highly-solicited avoiders (avoiders). Belonging to a cluster was independent of age, but was influenced by sex, with females being more represented in the 'inactive' cluster, and males in the 'active' cluster, whereas both sexes were equally represented in the 'avoider' cluster. Stability of piglets' allocation to specific clusters over age was high in the 'inactive' (59%) and 'active' (65%) clusters, but low in the 'avoider' cluster (7%). Haptoglobin and growth rate were higher in 'active' than 'inactive' pigs, and intermediate in 'avoiders'. Our findings suggest the existence of transient social styles in piglets, likely reflective of sexual dimorphism or health status