title: The deletion of STOP/MAP6 protein in mice triggers highly altered mood and impaired cognitive performances.
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.
authors.affiliation: INSERM UMRS 952, CNRS UMR 7224, Université Pierre et Marie Curie, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Fournet
authors.forename: Annie
authors.initials: A
authors.lastname: Schweitzer
authors.forename: Caroline
authors.initials: C
authors.lastname: Chevarin
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Deloulme
authors.forename: Michel
authors.initials: M
authors.lastname: Hamon
authors.forename: Bruno
authors.initials: B
authors.lastname: Giros
authors.forename: Annie
authors.initials: A
authors.lastname: Andrieux
authors.forename: Marie-Pascale
authors.initials: MP
authors.lastname: Martres
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D003072:Cognition Disorders / Q000235:genetics* / Q000378:metabolism / Q000523:psychology; D005260:Female; D017353:Gene Deletion; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D019964:Mood Disorders / Q000235:genetics* / Q000378:metabolism / Q000523:psychology; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology
chemical_list: D008869:Microtubule-Associated Proteins; C491893:Mtap6 protein, mouse; D009419:Nerve Tissue Proteins