The methylazoxymethanol acetate (MAM-E17) rat model: molecular and functional effects in the hippocampus.

TitleThe methylazoxymethanol acetate (MAM-E17) rat model: molecular and functional effects in the hippocampus.
Publication TypeJournal Article
Year of Publication2012
AuthorsHradetzky E, Sanderson TM, Tsang TM, Sherwood JL, Fitzjohn SM, Lakics V, Malik N, Schoeffmann S, O'Neill MJ, Cheng T M, Harris LW, Rahmoune H, Guest PC, Sher E, Collingridge GL, Holmes E, Tricklebank MD, Bahn S
JournalNeuropsychopharmacology
Volume37
Issue2
Pagination364-77
Date Published2012 Jan
ISSN1740-634X
KeywordsAnimals, Disease Models, Animal, Female, Frontal Lobe, Gene Expression Regulation, Hippocampus, Humans, Male, Metabolomics, Methylazoxymethanol Acetate, Pregnancy, Prenatal Exposure Delayed Effects, Proteomics, Rats, Schizophrenia, Synaptic Transmission
Abstract

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.

DOI10.1038/npp.2011.219
Alternate JournalNeuropsychopharmacology
PubMed ID21956444