The Methylazoxymethanol Acetate (MAM-E17) Rat Model: Molecular and Functional Effects in the Hippocampus
The Methylazoxymethanol Acetate (MAM-E17) Rat Model: Molecular and Functional Effects in the Hippocampus
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DOI：
10.1038/npp.2011.219
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发表时间：
2012-01-01
影响因子：
7.6
通讯作者：
Bahn, Sabine
中科院分区：
文献类型：
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作者：
Hradetzky, Eva;Sanderson, Thomas M.;Bahn, Sabine
在胚胎第17天(E17)给予DNA烷化剂甲氧基甲醇醋酸酯(MAM)会产生行为和解剖脑异常，这些异常是精神分裂症的某些方面的模型。这导致了MAM大鼠是精神分裂症的神经发育模型的前提。然而，在这个模型中影响的潜在分子通路还没有被阐明。在这项研究中，我们通过关注额叶皮质和海马区来研究成年MAM大鼠的分子表型，因为这些区域已知在精神分裂症中受到影响。蛋白质组学和代谢组学分析表明，MAM对E17的治疗主要导致海马谷氨酸能神经传递障碍，如一些精神分裂症患者。最重要的是，这些结果与我们发现的谷氨酸能神经传递功能缺陷是一致的，这是通过电生理记录确定的。因此，这项研究提供了第一个分子证据，结合功能验证，MAM-E17大鼠模型复制了与精神分裂症病理相关的海马区缺陷。《神经精神药理学》(2012年)37364-377；DOI：10.1038/npp.2011.219；2011年9月28日在线发布
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