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下丘脑蛋白质谱分析:社交挫败应激下的小鼠模型

Hypothalamic protein profiling from mice subjected to social defeat stress.

机构信息

Max Planck Institute of Psychiatry, Kraepelinstr 2-10, Munich, 80804, Germany.

CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Habsiguda, Hyderabad, 500007, India.

出版信息

Mol Brain. 2024 May 27;17(1):30. doi: 10.1186/s13041-024-01096-4.

Abstract

The Hypothalmic-Pituitary-Adrenal axis also known as the HPA axis is central to stress response. It also acts as the relay center between the body and the brain. We analysed hypothalamic proteome from mice subjected to chronic social defeat paradigm using iTRAQ based quantitative proteomics to identify changes associated with stress response. We identified greater than 2000 proteins after processing our samples analysed through Q-Exactive (Thermo) and Orbitrap Velos (Thermo) at 5% FDR. Analysis of data procured from the runs showed that the proteins whose levels were affected belonged primarily to mitochondrial and metabolic processes, translation, complement pathway among others. We also found increased levels of fibrinogen, myelin basic protein (MBP) and neurofilaments (NEFL, NEFM, NEFH) in the hypothalamus from socially defeated mice. Interestingly, research indicates that these proteins are upregulated in blood and CSF of subjects exposed to trauma and stress. Since hypothalamus secreted proteins can be found in blood and CSF, their utility as biomarkers in depression holds an impressive probability and should be validated in clinical samples.

摘要

下丘脑-垂体-肾上腺轴也被称为 HPA 轴,是应激反应的核心。它也是身体和大脑之间的中继中心。我们使用基于 iTRAQ 的定量蛋白质组学分析了经历慢性社交挫败模型的小鼠的下丘脑蛋白质组,以鉴定与应激反应相关的变化。在通过 Q-Exactive(Thermo)和 Orbitrap Velos(Thermo)在 5% FDR 下分析我们的样本后,我们鉴定出了超过 2000 种蛋白质。对从运行中获取的数据的分析表明,水平受影响的蛋白质主要属于线粒体和代谢过程、翻译、补体途径等。我们还发现,社交挫败的小鼠下丘脑的纤维蛋白原、髓鞘碱性蛋白(MBP)和神经丝(NEFL、NEFM、NEFH)水平升高。有趣的是,研究表明,这些蛋白质在暴露于创伤和应激的受试者的血液和 CSF 中上调。由于下丘脑分泌的蛋白质可以在血液和 CSF 中找到,因此它们作为抑郁症生物标志物的效用具有令人印象深刻的可能性,并且应该在临床样本中得到验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db72/11131206/c019864dba56/13041_2024_1096_Fig1_HTML.jpg

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