The Methylazoxymethanol Acetate (MAM-E17) Rat Model: Molecular and Functional Effects in the Hippocampus
Administration of the DNA-alkylating agent methylazoxymethanol acetate (MAM) on embryonic day 17 (E17) produces behavioral and anatomical brain abnormalities, which model 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 this study, we investigated the molecular phenotype of adult MAM rats by focusing on the frontal cortex and hippocampal areas, as these are known to be affected in schizophrenia. Proteomic and metabonomic analyses showed that the MAM treatment on E17 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.Neuropsychopharmacology advance online publication, 28 September 2011; doi:10.1038/npp.2011.219.
|animal models, schizophrenia, methylazoxymethanol acetate, hippocampus, electrophysiology, mass spectrometry|
|This work was funded by the European Commission 7th Framework Programme; grant id imi/115008 - Novel Methods leading to New Medications in Depression and Schizophrenia (NEWMEDS)|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
Hradetzky, E, Sanderson, T.M, Tsang, T.M, Sherwood, J.L, Fitzjohn, S.M, Lakics, V, … Bahn, S. (2012). The Methylazoxymethanol Acetate (MAM-E17) Rat Model: Molecular and Functional Effects in the Hippocampus. European Neuropsychopharmacology. doi:10.1038/npp.2011.219