Caractérisations biochimique anatomique et comportementale des souris dépourvues de la protéines STOP : un modèle expérimental pour l'étude de symptômes psycho-affectifs

Vincent Fournet 1
1 INSERM U836, équipe 1, Physiopathologie du cytosquelette
GIN - U836 - Grenoble Institut des Neurosciences
Abstract : The microtubule-associated STOP (MAP6) protein plays a key role in neuron architecture and synaptic plasticity, the dysfunctions of which are thought to be implicated in the pathophysiology of psychiatric diseases. In line with this hypothesis, the deletion of STOP in mice leads to neuroanatomical, biochemical and severe behavioral alterations, partly alleviated by antipsychotics. In the present study, we first examined the likely monoaminergic alterations in STOP KO mice. In mutant mice, serotonin (5-HT) and norepinephrin (NE) markers are accumulated in the midbrain and, in contrast, deeply depleted in all forebrain projection areas. Moreover, these monoaminergic imbalance were associated with a depression-like behavior, a decreased anxiety status and impairments in learning and memory tasks. The effects of a chronic treatment by fluoxetine or by epothilone D, a taxol microtubule-stabilizing compound, on the mood status of STOP KO mice were also characterized. Chronic fluoxetine treatment induced paradoxical effets on depressive and anxious status of STOP KO mice, depending on the paradigm used, and probably due to hypersensitivity to stress. On the other hand, both epothilone D and fluoxetine chronic treatments improved the short-term memory of STOP KO mice. Altogether, these data indicate that the deletion of STOP protein in mice caused deep alterations in mood and cognitive performances and that STOP protein might have a crucial role in the 5-HT and NE networks development.
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Agricultural sciences. Université de Grenoble, 2011. French. <NNT : 2011GRENV060>


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Vincent Fournet. Caractérisations biochimique anatomique et comportementale des souris dépourvues de la protéines STOP : un modèle expérimental pour l'étude de symptômes psycho-affectifs. Agricultural sciences. Université de Grenoble, 2011. French. <NNT : 2011GRENV060>. <tel-00656067>

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