THE METHYLAZOXYMETHANOL ACETATE (MAM-E17) RAT MODEL: MOLECULAR AND FUNCTIONAL EFFECTS IN THE HIPPOCAMPUS
Résumé
Administration of the DNA-alkylating agent methylazoxymethanol acetate (MAM) on embryonic day 17 (E17) produces behavioral and anatomical brain abnormalities modeling some aspects of schizophrenia. This has lead to the premise that MAM rats are a neurodevelopmental model for schizophrenia. However, the underlying molecular pathways affected in this model have not been elucidated. In the present study, we investigated the molecular phenotype of adult MAM rats in frontal cortex and hippocampus, which are affected in schizophrenia. Proteomic and metabonomic analyses showed that the MAM-treatment resulted primarily in deficits in hippocampal glutamatergic neurotransmission, as seen in some schizophrenia patients. Most importantly, these results were consistent with our finding of functional deficits in glutamatergic neurotransmission as identified using electrophysiological recordings. Thus, this study provides the first molecular evidence, combined with functional validation, that the MAM-E17 rat model reproduces hippocampal deficits relevant to the pathology of schizophrenia.
Origine : Fichiers produits par l'(les) auteur(s)
Loading...