自杀死亡的抑郁症患者脑细胞外囊泡的蛋白质组学改变与突触过程有关。

IF 4.5 2区 医学 Q1 CLINICAL NEUROLOGY
Pascal Ibrahim, Haruka Mitsuhashi, Lorne Taylor, Jenna Cleyle, Naguib Mechawar, Corina Nagy, Gustavo Turecki
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引用次数: 0

摘要

背景:重度抑郁障碍(MDD)是一种常见的衰弱性障碍,其分子神经生物学尚不清楚。细胞外囊泡(EVs)是细胞释放的小囊泡,参与细胞间通讯。它们携带生物活性分子,如蛋白质,反映其细胞起源的状态。在这项研究中,我们试图调查来自抑郁症个体的脑ev的蛋白质组学货物,将其与来自匹配的神经正常个体的ev进行比较。此外,我们研究了EV蛋白质组学货物如何与散装组织的蛋白质组学剖面进行比较。方法:采用质谱法和无标记定量法(LFQ)对86例个体前扣带皮层(ACC)样品的EV和大组织蛋白谱进行了研究。我们进行了差异表达分析以比较病例和对照组,随后进行了计算机分析以确定失调蛋白的潜在牵连功能。结果:与散装组织相比,ev显示出不同的蛋白质组学特征。差异表达分析显示,70种蛋白在MDD的EVs中有差异包装,而大组织中各组蛋白水平无显著差异。硅分析指出这些不同的EV蛋白在突触功能中的重要作用。结论:据我们所知,这是第一个研究抑郁症中EV蛋白的研究,为更好地理解重度抑郁症的病理生理提供了新的信息。这项工作为发现MDD的新治疗靶点铺平了道路,并促进了对MDD和其他精神疾病中EVs的更多研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Altered proteomics in brain extracellular vesicles from depressed individuals who died by suicide implicates synaptic processes.

Background: Major depressive disorder (MDD) is a common and debilitating disorder whose molecular neurobiology remains unclear. Extracellular vesicles (EVs) are small vesicles that are released by cells and are involved in intercellular communication. They carry bioactive molecules, such as proteins, that reflect the state of their cell of origin. In this study, we sought to investigate the proteomic cargo of brain EVs from depressed individuals as compared to EVs from matched neurotypical individuals. In addition, we investigated how the EV proteomic cargo compares to the proteomic profile of bulk tissue.

Methods: Using mass spectrometry and label-free quantification, we investigated the EV and bulk tissue protein profile from anterior cingulate cortex samples from 86 individuals. We performed differential expression analysis to compare cases and controls, followed by in silico analysis to determine potential implicated functions of dysregulated proteins.

Results: Extracellular vesicles display distinct proteomic profiles compared to bulk tissue. Differential expression analysis showed that 70 proteins were differentially packaged in EVs in MDD, while there was no significant difference in protein levels between groups in bulk tissue. In silico analysis points to a strong role of these differential EV proteins in synaptic functions.

Conclusion: To our knowledge, this is the first study to profile EV proteins in depression, providing novel information to better understand the pathophysiology of MDD. This work paves the way for discovering new therapeutic targets for MDD and prompts more investigations into EVs in MDD and other psychiatric disorders.

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来源期刊
CiteScore
8.40
自引率
2.10%
发文量
230
审稿时长
4-8 weeks
期刊介绍: The central focus of the journal is on research that advances understanding of existing and new neuropsychopharmacological agents including their mode of action and clinical application or provides insights into the biological basis of psychiatric disorders and thereby advances their pharmacological treatment. Such research may derive from the full spectrum of biological and psychological fields of inquiry encompassing classical and novel techniques in neuropsychopharmacology as well as strategies such as neuroimaging, genetics, psychoneuroendocrinology and neuropsychology.
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