The MAM-E17 neurodevelopmental model of schizophrenia

Abstract Schizophrenia is a neurodevelopmental disorder that could potentially be prevented before disease onset. However, knowledge about the mechanisms of schizophrenia development in the earlier stages of postnatal life, i.e., childhood and adolescence, is limited. Neurodevelopmental animal models of schizophrenia are useful for investigating schizophrenia before the appearance of symptoms. The MAM-E17 model is based on the prenatal administration of an environmental mitotoxin (methylazoxymethanol, MAM), which induces schizophrenia-like abnormalities in adulthood. The MAM-E17 model has good validity and could model the etiology, developmental trajectory, and therapy of schizophrenia. Impaired epigenetic regulations, i.e., changes in the dynamics of DNA or histone methylation, might be one of the mechanisms involved in the long-lasting abnormalities induced by prenatal environmental risk factors. Adolescence is a period sensitive to environmental conditions that might influence schizophrenia development. Moreover, some behavioral and neurochemical changes have already been observed in the MAM-E17 model, i.e., deficits in social interaction, abnormal GluN2B and CB1 receptor development in the medial prefrontal cortex and in parvalbumin interneurons in the hippocampus. Environmental factors in adolescence, i.e., social isolation or environmental enrichment, might alter the trajectory of brain development and the appearance of schizophrenia-like symptoms.