Díez-Vives Cristina, Gay Marina, García-Matas Silvia, Comellas Francesc, Carrascal Montserrat, Abian Joaquín, Ortega-Aznar Arantxa, Cristòfol Rosa, Sanfeliu Coral
Department of Brain Ischemia and Neurodegeneration, Institut d'Investigacions Biomèdiques de Barcelona, CSIC-IDIBAPS, Barcelona, Spain.
J Neurochem. 2009 Nov;111(4):945-55. doi: 10.1111/j.1471-4159.2009.06374.x. Epub 2009 Oct 7.
Senescence-accelerated prone (SAMP) strain 8 mice suffer an earlier development of cognitive age-related pathologies and a shorter life span than conventional mice. Protein alterations in astrocytes, in addition to those in neurons, may contribute to neurodegenerative damage. We applied proteomics techniques to study cell-specific early markers of brain aging-related degeneration in SAMP8. The two-dimensional protein expression patterns of the SAMP8 neuron and astrocyte cultures were compared with those obtained from senescence-accelerated resistant mouse strain 1 cultures. Differentially expressed spots were identified by matrix-assisted laser desorption/ionization-time of flight peptide map fingerprinting and database search. Proteins belonged to cell pathways of energy metabolism, biosynthesis, cell transduction and signaling, stress response, and the maintenance of cytoskeletal functions. Most of the changes were cell type specific. However, there was a general increase in cell transduction, signaling, and stress-related proteins and a decrease in cytoskeletal proteins. In addition, neurons showed an increased expression of proteins involved in biosynthetic pathways. A number of the protein alterations have been previously reported in the brain tissue proteome of SAMP8, aged brain or Alzheimer's disease brain. Alterations in neuron and astrocyte proteoma indicated that both cell types are involved in the brain degenerative changes of SAMP8 mice. However, network analysis suggests that neuronal changes are more complex and have a greater influence.
衰老加速易感性（SAMP）8品系小鼠比普通小鼠更早出现与年龄相关的认知病理变化，寿命也更短。除神经元中的蛋白质改变外，星形胶质细胞中的蛋白质改变可能也会导致神经退行性损伤。我们应用蛋白质组学技术研究SAMP8小鼠脑衰老相关退化的细胞特异性早期标志物。将SAMP8神经元和星形胶质细胞培养物的二维蛋白质表达模式与从衰老加速抗性小鼠1品系培养物中获得的模式进行比较。通过基质辅助激光解吸/电离飞行时间肽图指纹分析和数据库搜索来鉴定差异表达的斑点。这些蛋白质属于能量代谢、生物合成、细胞转导与信号传导、应激反应以及细胞骨架功能维持等细胞途径。大多数变化是细胞类型特异性的。然而，细胞转导、信号传导和应激相关蛋白质普遍增加，细胞骨架蛋白质减少。此外，神经元中参与生物合成途径的蛋白质表达增加。先前在SAMP8小鼠的脑组织蛋白质组、老年脑或阿尔茨海默病脑中已报道了许多蛋白质改变。神经元和星形胶质细胞蛋白质组的改变表明这两种细胞类型都参与了SAMP8小鼠的脑退行性变化。然而，网络分析表明神经元的变化更复杂，影响更大。
