1. Both chronic treatments by epothilone D and fluoxetine increase the short-term memory and differentially alter the mood status of STOP/MAP6 KO mice
- Author
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Vincent Fournet, Marie-Pascale Martres, Bruno Giros, Gaetan de Lavilléon, Annie Schweitzer, Annie Andrieux, INSERM U836, équipe 1, Physiopathologie du cytosquelette, Physiopathologie des Maladies du Système Nerveux Central, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe Physiopathologie du Cytosquelette (GPC), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF), Grants from INSERM and Université Pierre et Marie Curie, MENESR, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Grenoble Institut des Neurosciences (GIN)
- Subjects
Male ,Biochemistry ,MESH: Mice, Knockout ,stress ,Mice ,0302 clinical medicine ,microtubule-stabilizing compound ,Chronic stress ,MESH: Animals ,anxiety/depression ,Serotonin transporter ,Mice, Knockout ,0303 health sciences ,biology ,Depression ,MESH: Affect ,3. Good health ,MESH: Serotonin Uptake Inhibitors ,Memory, Short-Term ,Antidepressant ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Female ,Psychology ,Microtubule-Associated Proteins ,Selective Serotonin Reuptake Inhibitors ,medicine.drug ,medicine.medical_specialty ,Mice, 129 Strain ,MESH: Depression ,medicine.drug_class ,Antineoplastic Agents ,Serotonergic ,Anxiolytic ,MESH: Memory, Short-Term ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,MESH: Mice, 129 Strain ,MESH: Mice, Inbred C57BL ,Internal medicine ,Fluoxetine ,medicine ,MESH: Fluoxetine ,Animals ,MESH: Epothilones ,MESH: Mice ,030304 developmental biology ,antidepressant ,corticosterone ,serotonin/norepinephrine transporters ,MESH: Male ,Mice, Inbred C57BL ,MESH: Microtubule-Associated Proteins ,Affect ,Disease Models, Animal ,Endocrinology ,Anxiogenic ,Epothilones ,biology.protein ,MESH: Antineoplastic Agents ,Serotonin ,MESH: Disease Models, Animal ,MESH: Female ,030217 neurology & neurosurgery - Abstract
International audience; 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.
- Published
- 2012
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