Microtubule stabilizer ameliorates synaptic function and behavior in a mouse model for schizophrenia.

Abstract : BACKGROUND: Recent data suggest that cytoskeletal defects may play a role in schizophrenia. We previously imitated features of schizophrenia in an animal model by disrupting gene coding for a microtubule-associated protein called STOP. STOP-null mice display synaptic defects in glutamatergic neurons, hyper-dopaminergy, and severe behavioral disorders. Synaptic and behavioral deficits are amended by neuroleptic treatment in STOP-null mice, providing an attractive model to test new antipsychotic agents. We examined the effects of a taxol-related microtubule stabilizer, epothilone D. METHODS: Mice were treated either with vehicle alone or with epothilone D. Treatment effects on synaptic function were assessed using electron-microscopy quantification of synaptic vesicle pools and electrophysiology in the CA1 region of the hippocampus. Dopamine transmission was investigated using electrochemical assays. Behavior was principally assessed using tests of maternal skills. RESULTS: In STOP-null mice, treatment with epothilone D increased synaptic vesicle pools, ameliorated both short- and long-term forms of synaptic plasticity in glutamatergic neurons, and had a dramatic beneficial effect on mouse behavior. CONCLUSIONS: A microtubule stabilizer can have a beneficial effect on synaptic function and behavior, suggesting new possibilities for treatment of schizophrenia.
Type de document :
Article dans une revue
Biological Psychiatry, Elsevier, 2006, 60 (11), pp.1224-30. 〈10.1016/j.biopsych.2006.03.048〉
Liste complète des métadonnées

Littérature citée [34 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-00380045
Contributeur : Annie Andrieux <>
Soumis le : jeudi 7 mai 2009 - 14:44:56
Dernière modification le : jeudi 8 février 2018 - 11:08:22
Document(s) archivé(s) le : jeudi 10 juin 2010 - 19:58:04

Fichier

BioPsy_submit_file.pdf
Fichiers produits par l'(les) auteur(s)

Identifiants

Collections

Citation

Annie Andrieux, Paul Salin, Annie Schweitzer, Mélina Bégou, Bastien Pachoud, et al.. Microtubule stabilizer ameliorates synaptic function and behavior in a mouse model for schizophrenia.. Biological Psychiatry, Elsevier, 2006, 60 (11), pp.1224-30. 〈10.1016/j.biopsych.2006.03.048〉. 〈inserm-00380045〉

Partager

Métriques

Consultations de la notice

537

Téléchargements de fichiers

212