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Dernière publication 25/10/2012

Both chronic treatments by epothilone D and fluoxetine increase the short-term m

Recent evidence underlines the crucial role of neuronal cytoskeleton in the pathophysiology of psychiatric diseases. In this line, the deletion of...

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    [title] => Both chronic treatments by epothilone D and fluoxetine increase the short-term m
    [paragraph] => Both chronic treatments by epothilone D and fluoxetine increase the short-term memory and differentially alter the mood status of STOP/MAP6 KO mice
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Authors
Vincent Fournet, Gaetan de Lavilléon, Annie Schweitzer, Bruno Giros, Annie Andrieux, Marie-Pascale Martres


Lab
INSERM, Université Pierre et Marie Curie, Paris, France / Université Joseph Fourier, Grenoble, France

Journal
Journal of Neurochemistry

Abstract
Recent evidence underlines the crucial role of neuronal cytoskeleton in the pathophysiology of psychiatric diseases. In this line, the deletion of STOP/MAP6 (Stable Tubule Only Polypeptide), a microtubule-stabilizing protein, triggers various neurotransmission and behavioral defects, suggesting that STOP knockout (KO) mice could be a relevant experimental model for schizoaffective symptoms. To establish the predictive validity of such a mouse line, in which the brain serotonergic tone is dramatically imbalanced, the effects of a chronic fluoxetine treatment on the mood status of STOP KO mice were characterized. Moreover, we determined the impact, on mood, of a chronic treatment by epothilone D, a taxol-like microtubule-stabilizing compound that has previously been shown to improve the synaptic plasticity deficits of STOP KO mice. We demonstrated that chronic fluoxetine was either antidepressive and anxiolytic, or pro-depressive and anxiogenic, depending on the paradigm used to test treated mutant mice. Furthermore, control-treated STOP KO mice exhibited paradoxical behaviors, compared with their clear-cut basal mood status. Paradoxical fluoxetine effects and control-treated STOP KO behaviors could be because of their hyper-reactivity to acute and chronic stress. Interestingly, both epothilone D and fluoxetine chronic treatments improved the short-term memory of STOP KO mice. Such treatments did not affect the serotonin and norepinephrine transporter densities in cerebral areas of mice. Altogether, these data demonstrated that STOP KO mice could represent a useful model to study the relationship between cytoskeleton, mood, and stress, and to test innovative mood treatments, such as microtubule-stabilizing compounds.

BIOSEB Instruments Used
Tail Suspension Test - Wireless (BIO-TST5)

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La version 5 du Test de Suspension Caudale de Bioseb, basée sur des capteurs de force ainsi que sur de l'acquisition vidéo, est la seule et unique solution totalement automatisée au monde pour effectuer un test de désespoir comportemental simple et objectif sur souris. Il s'agit d'une méthode rapide, fiable et sans douleur pour tester les effets psychotropes de drogues et substances comme les antidépresseurs et les sédatifs. Ce test classique et indolore pour la recherche sur l'anxiété et la dépression est désormais présenté avec un nouveau logiciel puissant et moderne, dans une version sans-fil BlueTooth.

Instrument for mice

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