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The deletion of STOP/MAP6 protein in mice triggers highly altered mood and impaired cognitive performances.

Vincent Fournet 1 Annie Schweitzer 2 Caroline Chevarin 3 Jean-Christophe Deloulme 2 Michel Hamon 3 Bruno Giros 4 Annie Andrieux 5 Marie-Pascale Martres 4, *
* Corresponding author
1 INSERM U836, équipe 1, Physiopathologie du cytosquelette
Physiopathologie des Maladies du Système Nerveux Central, GIN - Grenoble Institut des Neurosciences
2 INSERM U836, équipe 1, Physiopathologie du cytosquelette
GIN - Grenoble Institut des Neurosciences
5 INSERM U836, équipe 1, Physiopathologie du cytosquelette
GPC - Groupe Physiopathologie du Cytosquelette, GIN - Grenoble Institut des Neurosciences
Abstract : The microtubule-associated Stable Tubulie Only Polypeptide (STOP; also known as 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. The deletion of STOP in mice leads to severe disorders reminiscent of several schizophrenia-like symptoms, which are also associated with differential alterations of the serotonergic tone in somas versus terminals. In STOP knockout (KO) compared with wild-type mice, serotonin (5-HT) markers are found to be markedly accumulated in the raphe nuclei and, in contrast, deeply depleted in all serotonergic projection areas. In the present study, we carefully examined whether the 5-HT imbalance would lead to behavioral consequences evocative of mood and/or cognitive disorders. We showed that STOP KO mice exhibited depression-like behavior, associated with a decreased anxiety-status in validated paradigms. In addition, although STOP KO mice had a preserved very short-term memory, they failed to perform well in all other learning and memory tasks. We also showed that STOP KO mice exhibited regional imbalance of the norepinephrine tone as observed for 5-HT. As a consequence, mutant mice were hypersensitive to acute antidepressants with different selectivity. 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 norepinephrine networks development.
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Submitted on : Monday, September 24, 2012 - 12:12:33 PM
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Vincent Fournet, Annie Schweitzer, Caroline Chevarin, Jean-Christophe Deloulme, Michel Hamon, et al.. The deletion of STOP/MAP6 protein in mice triggers highly altered mood and impaired cognitive performances.. Journal of Neurochemistry, Wiley, 2012, 121 (1), pp.99-114. ⟨10.1111/j.1471-4159.2011.07615.x⟩. ⟨inserm-00734692⟩

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