Rite I, Argüelles S, Venero J L, García-Rodriguez S, Ayala A, Cano J, Machado A
Departamento de Bioquímica, Bromatología y Toxicología, Facultad de Farmacia, Universidad de Sevilla, C/Prof. Garcia Gonzalez 2, Seville, Spain.
J Neurosci Res. 2007 Dec;85(16):3607-18. doi: 10.1002/jnr.21452.
We have performed proteomic analysis in the cerebrospinal fluid in an animal model of Parkinson's disease induced by axotomy of the medial forebrain bundle. In this model, the degeneration of dopaminergic neurons was completed in 14 days, with a loss of about 50% dopaminergic neurons in the substantia nigra and a loss of more than 80% dopamine terminals in the striatum, with a similar diminution of dopamine levels in both structures. Proteins were separated by 2D electrophoresis and identified by matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF). We found significant increases of haptoglobin and transthyretin along with a decrease of Apo E concentrations in the cerebrospinal fluid of axotomized animals. Changes for haptoglobin and transthyretin were further confirmed in cerebrospinal fluid and plasma by Western blotting. These results suggest that monitoring plasma levels of these signals appears to be a promising biological marker of neuronal degeneration of the nigrostriatal dopaminergic system.
我们在通过切断内侧前脑束诱导的帕金森病动物模型中，对脑脊液进行了蛋白质组学分析。在该模型中，多巴胺能神经元的变性在14天内完成，黑质中约50%的多巴胺能神经元丢失，纹状体中80%以上的多巴胺终末丢失，两个结构中的多巴胺水平也有类似程度的降低。蛋白质通过二维电泳分离，并通过基质辅助激光解吸电离飞行时间质谱（MALDI-TOF）进行鉴定。我们发现，在切断轴突的动物的脑脊液中，触珠蛋白和转甲状腺素蛋白显著增加，同时载脂蛋白E浓度降低。通过蛋白质免疫印迹法在脑脊液和血浆中进一步证实了触珠蛋白和转甲状腺素蛋白的变化。这些结果表明，监测这些信号的血浆水平似乎是黑质纹状体多巴胺能系统神经元变性的一个有前景的生物标志物。
