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Schizophrenia: validity of a 3-hit mouse model

Abstract : Schizophrenia is a frequent psychiatric disease (prevalence 1%). Unfortunately, current treatments are unsatisfactory: they do not cover the entirety of symptoms, they can even worsen them, and they are inefficient in 30% of patients. There is a crucial need for new drugs, which requires more relevant animal models taking into account the multifactorial nature of this pathology. We built a new animal model gathering three factors: a genetic predisposition (partial deletion of the MAP6 (Microtubule-Associated Protein 6) with an early post-natal stress (maternal separation at the age of 9 days during 24h) and a late disturbance during adolescence (THC from post-natal day 32 to 52; 8 mg/kg). A particular focus was made on behavior, brain imaging, and immunohistochemistry. The 3-hit combination induces specific decrease in spontaneous activity in the open-field, in sociability in the approach-avoidance test, and in working memory performances. In vivo and post-mortem MRI revealed a decrease in cortical thickness and in hippocampus volume, and a loss of integrity of callosal fibers (less axons, less myelin). Moreover, a decrease in density of parvalbumin-positive neurons was observed in CA1 of hippocampus. To conclude, 3-hit combination causes several symptoms mimicking negative and cognitive symptoms of schizophrenia, accompanied with structural changes bringing a high face validity. Moreover, it possesses a strong construct validity which fits with gene x environment interactions hypothesis of schizophrenia. The predictive validity is currently investigated by using lurasidone. The model is expected to be a powerful tool to test new therapeutic strategies for the treatment of schizophrenia.
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Contributeur : Solenn Percelay <>
Soumis le : mardi 21 mai 2019 - 13:29:56
Dernière modification le : vendredi 27 mars 2020 - 02:19:49


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  • HAL Id : hal-02135529, version 1


Solenn Percelay, Thomas Freret, Boubacar Diarra, Nicolas Delcroix, Elise Leroux, et al.. Schizophrenia: validity of a 3-hit mouse model. 11th Federation of European Neuroscience Societies Forum of Neuroscience, Jul 2018, Berlin, Germany. 2018. ⟨hal-02135529⟩



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