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重度抑郁症动物模型中的外周生物标志物。

Peripheral biomarkers in animal models of major depressive disorder.

机构信息

Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, Via Irnerio 48, 40126 Bologna, Italy.

出版信息

Dis Markers. 2013;35(1):33-41. doi: 10.1155/2013/284543. Epub 2013 Jul 21.

Abstract

Investigations of preclinical biomarkers for major depressive disorder (MDD) encompass the quantification of proteins, peptides, mRNAs, or small molecules in blood or urine of animal models. Most studies aim at characterising the animal model by including the assessment of analytes or hormones affected in depressive patients. The ultimate objective is to validate the model to better understand the neurobiological basis of MDD. Stress hormones or inflammation-related analytes associated with MDD are frequently measured. In contrast, other investigators evaluate peripheral analytes in preclinical models to translate the results in clinical settings afterwards. Large-scale, hypothesis-free studies are performed in MDD models to identify candidate biomarkers. Other studies wish to propose new targets for drug discovery. Animal models endowed with predictive validity are investigated, and the assessment of peripheral analytes, such as stress hormones or immune molecules, is comprised to increase the confidence in the target. Finally, since the mechanism of action of antidepressants is incompletely understood, studies investigating molecular alterations associated with antidepressant treatment may include peripheral analyte levels. In conclusion, preclinical biomarker studies aid the identification of new candidate analytes to be tested in clinical trials. They also increase our understanding of MDD pathophysiology and help to identify new pharmacological targets.

摘要

用于重度抑郁症(MDD)的临床前生物标志物的研究包括在动物模型的血液或尿液中定量检测蛋白质、肽、mRNA 或小分子。大多数研究旨在通过评估受抑郁患者影响的分析物或激素来描述动物模型。最终目标是验证该模型,以更好地理解 MDD 的神经生物学基础。经常测量与 MDD 相关的应激激素或炎症相关分析物。相比之下,其他研究人员在临床前模型中评估外周分析物,以便随后将结果转化到临床环境中。在 MDD 模型中进行了大规模的、无假设的研究,以确定候选生物标志物。其他研究希望为药物发现提出新的靶点。研究具有预测有效性的动物模型,并评估应激激素或免疫分子等外周分析物,以提高对目标的信心。最后,由于抗抑郁药的作用机制尚不完全清楚,因此研究与抗抑郁治疗相关的分子变化可能包括外周分析物水平。总之,临床前生物标志物研究有助于确定新的候选分析物,以便在临床试验中进行测试。它们还增加了我们对 MDD 病理生理学的理解,并有助于确定新的药理学靶点。

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