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Etude anatomique et fonctionnelle du cerveau des souris KO STOP : modèle animal pour l'étude de la schizophrénie

Abstract : My thesis work was dedicated to the characterization of neuro-developmental cellular and molecular events at the basis of schizophrenia. Using an animal model for schizophrenia (STOP-null mice), I have searched for relationships between whole-brain volume loss and in situ neuronal biology that could be responsible for this defect. Hence, quantitative Western blot analysis was performed and demonstrated that STOP-null mice whole-brain volume reduction was strongly associated with decreased expression of axonal, myelinic and synaptic markers. Moreover, histological data showed that tracts of the limbic system were altered in STOP-null mice, e.g. the ventral part of the fornix - connecting the hippocampus to the mammillary body - was missing. It is also strongly altered in schizophrenic patients. Finally, it was obvious that STOP-null fornical axons were disorganized in their ventral part, thus promoting extinction of the tract, using lentiviral fornix tracings. Using the same model, I also analysed hippocampal adult neurogenesis. That process is specifically and progressively altered in STOP-null mice. Dendritic architecture of immature hippocampal neurons seemed to be abnormal: immature STOP-null neurons exhibited a longer primary dendrite and a more branched dendritic tree than wild-type immature neurons. Retroviral labelling of hippocampal neural stem cells showed a reduction of STOP-null immature neurons 4 weeks post-infection, suggesting a precocious maturation of newly generated immature neurons. This work opens new research outlook about embryonic fornix development and overall about brain neuronal connectivities. Moreover, we will analyse axonal and synaptic maturation of hippocampal immature neurons, process important for development of neuronal connectivity.
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Contributor : Marion Jany <>
Submitted on : Monday, February 21, 2011 - 3:11:13 PM
Last modification on : Friday, November 6, 2020 - 3:44:04 AM
Long-term archiving on: : Tuesday, November 6, 2012 - 2:35:10 PM


  • HAL Id : tel-00567610, version 1


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Marion Jany. Etude anatomique et fonctionnelle du cerveau des souris KO STOP : modèle animal pour l'étude de la schizophrénie. Neurosciences [q-bio.NC]. Université de Grenoble, 2010. Français. ⟨tel-00567610⟩



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