Neurosciences CEDD, GlaxoSmithKline, Verona, Italy.
Prog Neuropsychopharmacol Biol Psychiatry. 2010 Aug 16;34(6):1037-48. doi: 10.1016/j.pnpbp.2010.05.019. Epub 2010 May 23.
Availability of peripheral biomarkers for depression could aid diagnosis and help to predict treatment response. The objective of this work was to analyse the peripheral biomarker response in a gene-environment interaction model of depression. Genetically selected Flinders Sensitive Line (FSL) rats were subjected to maternal separation (MS), since early-life trauma is an important antecedent of depression. An open-ended approach based on a proteomic analysis of serum was combined with the evaluation of depression-associated proteins.
Rats experienced MS and chronically received escitalopram (ESC) or nortryptiline (NOR). Serum proteins were compared by two-dimensional gel electrophoresis. Corticosterone, cytokines, BDNF and C-reactive protein (CRP) were measured by immunoassays.
Comparing FSL with the control Flinders Resistant Line (FRL), Apo-AI and Apo-AIV, alpha1-macroglobulin, glutathione peroxidase and complement-C3 were significantly modulated. Significant increases were detected in leptin, interleukin (IL) 1alpha and BDNF. CRP levels were significantly reduced. The impact of early-life stress was assessed by comparing FSL+MS versus FSL. Apo-E, alpha1-macroglobulin, complement-C3, transferrin and hemopexin were significantly modulated. The effect of stress in antidepressant response was then evaluated. In the comparison FSL+ESC+MS versus FSL+ESC, albumin, alpha1-macroglobulin, glutathione peroxidase and complement-C3 were modulated and significant reductions were detected in IL4, IL6, IL10, CRP and BDNF. By comparing FSL+NOR+MS versus FSL+NOR proteins like Apo-AIV, pyruvate dehydrogenase, alpha1-macroglobulin, transferrin and complement-C3 showed different levels.
Lipid metabolism and immunity proteins were differently expressed in FSL in comparison with FRL. Exposure to MS induced changes in inflammation and transport proteins which became apparent in response to antidepressant treatments. Modulated proteins could suggest biomarker studies in humans.
抑郁症外周生物标志物的可用性可以辅助诊断并有助于预测治疗反应。本研究的目的是分析抑郁症基因-环境相互作用模型中的外周生物标志物反应。选择弗林德斯敏感系（FSL）大鼠进行母体分离（MS），因为生命早期创伤是抑郁症的重要前兆。基于血清的蛋白质组学分析的开放式方法与评估与抑郁相关的蛋白质相结合。
MS 处理的大鼠长期接受艾司西酞普兰（ESC）或去甲替林（NOR）治疗。通过二维凝胶电泳比较血清蛋白。通过免疫测定法测量皮质酮、细胞因子、BDNF 和 C 反应蛋白（CRP）。
与对照弗林德斯抗性系（FRL）相比，FSL 中载脂蛋白 AI 和 AIV、α1-巨球蛋白、谷胱甘肽过氧化物酶和补体 C3 显著调节。瘦素、白细胞介素（IL）1α和 BDNF 水平显著升高。CRP 水平显著降低。通过比较 FSL+MS 与 FSL 来评估生命早期应激的影响。载脂蛋白 E、α1-巨球蛋白、补体 C3、转铁蛋白和血红素结合蛋白显著调节。然后评估应激在抗抑郁反应中的作用。在 FSL+ESC+MS 与 FSL+ESC 的比较中，白蛋白、α1-巨球蛋白、谷胱甘肽过氧化物酶和补体 C3 被调节，IL4、IL6、IL10、CRP 和 BDNF 水平显著降低。通过比较 FSL+NOR+MS 与 FSL+NOR，载脂蛋白 AIV、丙酮酸脱氢酶、α1-巨球蛋白、转铁蛋白和补体 C3 等蛋白显示出不同的水平。
与 FRL 相比，FSL 中的脂质代谢和免疫蛋白表达不同。暴露于 MS 会引起炎症和转运蛋白的变化，这些变化在抗抑郁治疗中变得明显。调节蛋白可提示人类进行生物标志物研究。
