The Methylazoxymethanol Acetate (MAM-E17) Rat Model: Molecular and Functional Effects in the Hippocampus

E Hradetzky, Tom M Sanderson, T M Tsang, J L Sherwood, Stephen M Fitzjohn, V Lakics, N Malik, S Schoeffmann, M J O'Neill, T M Cheng, L W Harris, H Rahmoune, P C Guest, E Sher, GL Collingridge, E Holmes, M D Tricklebank, S Bahn

Research output: Contribution to journalArticle (Academic Journal)peer-review

41 Citations (Scopus)

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.
Translated title of the contributionThe Methylazoxymethanol Acetate (MAM-E17) Rat Model: Molecular and Functional Effects in the Hippocampus
Original languageEnglish
Pages (from-to)364 - 377
Number of pages13
JournalNeuropsychopharmacology
Volume37
DOIs
Publication statusPublished - Jan 2012

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