Vercauteren Freya G G, Flores Gonzalo, Ma Weiya, Chabot Jean-Guy, Geenen Lieve, Clerens Stefan, Fazel Ali, Bergeron John J M, Srivastava Lalit K, Arckens Lutgarde, Quirion Rémi
Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montréal, Québec, Canada.
Proteomics. 2007 Oct;7(19):3569-79. doi: 10.1002/pmic.200700379.
Limited information is currently available on molecular events that underlie schizophrenia-like behaviors in animal models. Accordingly, we developed an organelle proteomic approach enabling the study of neurotransmission-related proteins in the prefrontal cortex (PFC) of postpubertal (postnatal day 60 (PD60)) neonatally ventral hippocampal (nVH) lesioned rats, an extensively used neurodevelopmental model of schizophrenia-like behaviors. The PFC was chosen because of its purported role in the etiology of the disease. Statistical analysis of 392 reproducible spots on 2-D organelle proteomic patterns revealed significant changes in intensity of 18 proteinous spots in plasma membrane-enriched fractions obtained from postpubertal nVH lesioned rats compared to controls. Mass spectrometric analysis and database searching allowed the identification of a single protein in each of the nine differential spots, including proteins of low abundance, such as neurocalcin delta. Most of the identified dysregulated proteins, including clathrin light chain B, syntaxin binding protein 1b and visinin-like protein 1 are known to be linked to various neurotransmitter systems and to play key roles in plasma membrane receptor expression and recycling as well as synaptic vesicle exocytosis/recycling. Organelle proteomic approaches have hence proved to be most useful to identify key proteins linked to a given behavior in animal models of brain diseases.
目前关于动物模型中精神分裂症样行为背后的分子事件的信息有限。因此，我们开发了一种细胞器蛋白质组学方法，用于研究青春期后（出生后第60天（PD60））新生腹侧海马（nVH）损伤大鼠前额叶皮质（PFC）中与神经传递相关的蛋白质，这是一种广泛使用的精神分裂症样行为神经发育模型。选择PFC是因为它在该疾病的病因学中据称具有作用。对二维细胞器蛋白质组学模式上的392个可重复斑点进行统计分析后发现，与对照组相比，青春期后nVH损伤大鼠富含质膜的组分中18个蛋白质斑点的强度有显著变化。质谱分析和数据库搜索使得能够在九个差异斑点中的每一个中鉴定出一种蛋白质，包括低丰度蛋白质，如神经钙蛋白δ。大多数已鉴定出的失调蛋白质，包括网格蛋白轻链B、 syntaxin结合蛋白1b和类视黄醛蛋白1，已知与各种神经递质系统有关，并在质膜受体表达和循环以及突触小泡胞吐/循环中起关键作用。因此，细胞器蛋白质组学方法已被证明对于在脑部疾病动物模型中鉴定与特定行为相关的关键蛋白质最为有用。
