社会挫败应激小鼠下丘脑蛋白质图谱分析

IF 3.3 3区 医学 Q2 NEUROSCIENCES Molecular Brain Pub Date : 2024-05-27 DOI:10.1186/s13041-024-01096-4
Shiladitya Mitra, Ghantasala S Sameer Kumar, Anumita Samanta, Mathias V Schmidt, Suman S Thakur
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引用次数: 0

摘要

下丘脑-垂体-肾上腺轴(又称 HPA 轴)是压力反应的核心。它也是身体和大脑之间的中继中心。我们利用基于 iTRAQ 的定量蛋白质组学分析了长期社会挫败范式下小鼠的下丘脑蛋白质组,以确定与应激反应相关的变化。通过Q-Exactive(Thermo)和Orbitrap Velos(Thermo)在5% FDR条件下对样本进行分析处理后,我们鉴定出了2000多种蛋白质。对运行数据的分析表明,水平受到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,在社交失败小鼠的下丘脑中,纤维蛋白原、髓鞘碱性蛋白(MBP)和神经丝(NEFL、NEFM、NEFH)的含量也有所增加。有趣的是,研究表明,这些蛋白质在遭受创伤和压力的受试者的血液和脑脊液中上调。由于下丘脑分泌蛋白可在血液和脑脊液中发现,它们作为抑郁症生物标志物的可能性很大,应在临床样本中进行验证。
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Hypothalamic protein profiling from mice subjected to social defeat stress.

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.

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来源期刊
Molecular Brain
Molecular Brain NEUROSCIENCES-
CiteScore
7.30
自引率
0.00%
发文量
97
审稿时长
>12 weeks
期刊介绍: Molecular Brain is an open access, peer-reviewed journal that considers manuscripts on all aspects of studies on the nervous system at the molecular, cellular, and systems level providing a forum for scientists to communicate their findings. Molecular brain research is a rapidly expanding research field in which integrative approaches at the genetic, molecular, cellular and synaptic levels yield key information about the physiological and pathological brain. These studies involve the use of a wide range of modern techniques in molecular biology, genomics, proteomics, imaging and electrophysiology.
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