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, la chance de participer a la mise en place d'un brevet portant sur un composé modulant le gradient aux ions chlorures que je nommerai composé X. Pour ce brevet nous avons testé l'effet du composé X et du bumétanide sur les comportements autistiques de trois modèle d'autisme: les souris FMR1-, OPRM1-et SHANK3-. Dans le cadre de ma thèse je vais présenter certains des résultats auxquels j'ai participé
, Les protocoles des tests réalisés ici sont similaires à ceux réalisés dans le deuxième article. Animaux: Souris ne présentant pas le récpteur au opïoides mu
, Les souris sont stabulées en groupe (2 à 5 par cage) et maintenue sous un cycle jour/nuit de 12 heures (jour à 7h00) à une température contrôlée à 21±1°C
, Souris ne présentant pas le gène Fmr1
, Les souris sont stabulées en groupe (2 à 5 par cage) et maintenues sous un cycle jour/nuit de 12 heures (jour à 7h00) à une température contrôlée à 21±1°C, La lignée des souris Fmr1 a été fournie par Rob Willemsen (Erasmus MC
, 205 et 500 mg/kg versus saline) montre un effet bénéfique dépendant de la dose, augmentant, dans le modèle Oprm1 -/-, le temps total passé en contact social, le traitement avec le composé, vol.125
, Ce traitement n'a pas d'effet significatif sur le nombre de contact de museaux (effet génotype: F 1,59 =7.8, p<0.01; effet dose: F 1,59 =5.8, p<0.001; génotype x dose: F 1,59 =5.2, p<0.05) et le nombre de contact aux pattes (effet génotype: F 1,59 =46.7, p<0.0001; effet dose: F 1,59 =13.0, p<0.05; génotype x dose: F 1,59 =9.6, p<0.01), le temps passé en contact aux pattes (effet génotype: F 1,59 =22.9, p<0.0001; effet dose: F 1,59 =6.0, p<0.05; génotype x dose: F 1,59 =5.2, p<0.05) et la durée des contacts aux pattes
, 0001) chez les animaux mutant (Figure 2). Ainsi, le traitement au bumétanide réduit efficacement les stéréotypies motrices chez les souris Oprm1
, Figure 2 : Effets du traitement avec le composé (125, 250, 500 mg/kg) ainsi que du
, Les données sont présentées comme moyenne ± sem. Différence par rapport aux contrôles salins : une étoile: p<0.05, Bumétanide (0.5 mg/kg) sur les comportements stéréotypés
, La dose intermédiaire de 250 mg/kg a été choisi pour être tester sur d'autres modèles car elle a démontré son efficacité à soulager les symptômes autistiques chez les souris Oprm1 -/-. Je vais ici présenter certains résultats obtenue chez la souris Fmr1
, Dans le test d'interaction social direct (Figure 3A), le traitement avec le composé à 250 mg/kg normalise le temps passé, en contact social direct
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