The Methylazoxymethanol Acetate (MAM-E17) Rat Model: Molecular and Functional Effects in the Hippocampus
| Autor: | Graham L. Collingridge, Viktor Lakics, Tammy M. K. Cheng, Stephen M. Fitzjohn, John L. Sherwood, Nadia Malik, Sabine Bahn, Hassan Rahmoune, Thomas M. Sanderson, Mark D. Tricklebank, Elaine Holmes, Emanuele Sher, Tsz M. Tsang, Michael J. O'Neill, Stephanie Schoeffmann, Eva Hradetzky, Laura W. Harris, Paul C. Guest |
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| Přispěvatelé: | Mass Spectrometry Unit [Rehovot ] (ISMS), Weizmann Institute of Science [Rehovot, Israël], Neurosciences |
| Rok vydání: | 2011 |
| Předmět: |
Hippocampus
Neurotransmission Hippocampal formation 03 medical and health sciences Glutamatergic chemistry.chemical_compound 0302 clinical medicine mental disorders medicine Antipsychotics Biological Psychiatry 030304 developmental biology Pharmacology 0303 health sciences Methylazoxymethanol acetate Molecular screening Mass spectrometry medicine.disease Animal models 3. Good health Electrophysiology Psychiatry and Mental health Frontal lobe chemistry MAM Schizophrenia [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology Psychology Neuroscience 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Neuropsychopharmacology Neuropsychopharmacology, Nature Publishing Group, 2011, ⟨10.1038/npp.2011.219⟩ Neuropsychopharmacology, 37(2), 364-377. Nature Publishing Group |
| ISSN: | 1740-634X 0893-133X 0007-0920 |
| DOI: | 10.1038/npp.2011.219 |
| Popis: | 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 (2012) 37, 364-377; doi:10.1038/npp.2011.219; published online 28 September 2011 |
| Databáze: | OpenAIRE |
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