title: The methylazoxymethanol acetate (MAM-E17) rat model: molecular and functional effects in the hippocampus.
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.
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK.
authors.forename: Eva
authors.initials: E
authors.lastname: Hradetzky
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Sanderson
authors.forename: Tsz M
authors.initials: TM
authors.lastname: Tsang
authors.forename: John L
authors.initials: JL
authors.lastname: Sherwood
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Fitzjohn
authors.forename: Viktor
authors.initials: V
authors.lastname: Lakics
authors.forename: Nadia
authors.initials: N
authors.lastname: Malik
authors.forename: Stephanie
authors.initials: S
authors.lastname: Schoeffmann
authors.forename: Michael J
authors.initials: MJ
authors.lastname: O'Neill
authors.forename: Tammy Mk
authors.initials: TM
authors.lastname: Cheng
authors.forename: Laura W
authors.initials: LW
authors.lastname: Harris
authors.forename: Hassan
authors.initials: H
authors.lastname: Rahmoune
authors.forename: Paul C
authors.initials: PC
authors.lastname: Guest
authors.forename: Emanuele
authors.initials: E
authors.lastname: Sher
authors.forename: Graham L
authors.initials: GL
authors.lastname: Collingridge
authors.forename: Elaine
authors.initials: E
authors.lastname: Holmes
authors.forename: Mark D
authors.initials: MD
authors.lastname: Tricklebank
authors.forename: Sabine
authors.initials: S
authors.lastname: Bahn
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D008297:Male; D055432:Metabolomics / Q000379:methods; D008746:Methylazoxymethanol Acetate / Q000494:pharmacology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism* / Q000503:physiopathology; D040901:Proteomics / Q000379:methods; D051381:Rats; D012559:Schizophrenia / Q000139:chemically induced* / Q000378:metabolism* / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D008746:Methylazoxymethanol Acetate