Phenotyping extracellular vesicles and their serotonin transporter cargo in major depressive disorder

IF 4.9 2区医学 Q1 CLINICAL NEUROLOGY

Journal of affective disorders Pub Date : 2025-06-21 DOI:10.1016/j.jad.2025.119740

Łukasz Zadka , Benjamin Eggerstorfer , Igor Buzalewicz , Chrysoula Vraka , Agnieszka Rusak , Godber M. Godbersen , Agnieszka Opalińska , Jakob Unterholzner , Agnieszka Ulatowska-Jarża , Cecile Philippe , Katarzyna Haczkiewicz-Leśniak , Leo R. Silberbauer , Matej Murgaš , Lukas Nics , Andreas Hahn , Marcus Hacker , Agnieszka Gomułkiewicz , Dan Rujescu , Marzenna Podhorska-Okołów , Rupert Lanzenberger , Gregor Gryglewski

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引用次数: 0

Abstract

With their ability to cross the blood-brain barrier, transport and regulate the release of various signaling molecules, extracellular vesicles (EVs) constitute a novel avenue to study intercellular communication in various pathologies, including psychiatric disorders. We studied 34 major depressive disorder (MDD) patients and 57 healthy controls and characterized EVs isolated from plasma using digital holographic tomography (DHT) and nanoparticle tracking analysis (NTA). EVs detected in DHT were markedly smaller and less variable in size in MDD patients. Furthermore, a lower variance of refractive indices related to the dry mass density of EVs was observed in patients. Meanwhile, NTA revealed a trend for elevated concentration of EVs in MDD. In DHT, EV dimensions correlated with plasma mRNA expression of exosomal markers CD63 and CD9, with corresponding alterations in MDD. Levels of EV concentration and CD9 were both negatively correlated with antidepressant treatment response. Utilizing electron microscopy and immunoblots we confirmed the presence of serotonin transporters (SERT) as EV cargo. SERT levels in EVs correlated with cerebral SERT binding potential in the amygdala measured using positron emission tomography. Next to the implication of altered EV communication in mood disorders, the pronounced differences in plasma EV characteristics and exosomal markers in MDD might inform the development of assays with diagnostic or prognostic value for clinical practice.

ClinicalTrials.gov

Patient Stratification and Treatment Response Prediction in Neuropharmacotherapy Using Hybrid Positron Emmission Tomography/Magnetic Resconance Imaging (PET/MR); https://clinicaltrials.gov/study/NCT02711215; NCT02711215.

查看原文本刊更多论文

重度抑郁症细胞外囊泡及其血清素转运体的表型分析。

细胞外囊泡（EVs）具有穿越血脑屏障、运输和调节各种信号分子释放的能力，为研究包括精神疾病在内的各种疾病的细胞间通讯提供了新的途径。我们研究了34例重度抑郁症（MDD）患者和57名健康对照者，并使用数字全息断层扫描（DHT）和纳米颗粒跟踪分析（NTA）对从血浆中分离的ev进行了表征。在重度抑郁症患者中，DHT检测到的EVs明显更小，大小变化较小。此外，在患者中观察到与ev干质量密度相关的折射率方差较低。与此同时，NTA显示了MDD地区ev浓度升高的趋势。在DHT中，EV尺寸与血浆外泌体标志物CD63和CD9的mRNA表达相关，在MDD中也有相应的变化。EV浓度和CD9水平均与抗抑郁治疗反应呈负相关。利用电子显微镜和免疫印迹，我们证实了血清素转运体（SERT）作为EV货物的存在。使用正电子发射断层扫描测量ev中的SERT水平与杏仁核中大脑SERT结合电位相关。除了情绪障碍中EV通信改变的含义外，MDD中血浆EV特征和外泌体标志物的显著差异可能会为临床实践提供具有诊断或预后价值的检测方法。临床试验。使用正电子发射断层扫描/磁共振混合成像（PET/MR）进行神经药物治疗的患者分层和治疗反应预测；https://clinicaltrials.gov/study/NCT02711215;NCT02711215。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of affective disorders 医学-精神病学

CiteScore

10.90

自引率

6.10%

发文量

1319

审稿时长

9.3 weeks

期刊介绍： The Journal of Affective Disorders publishes papers concerned with affective disorders in the widest sense: depression, mania, mood spectrum, emotions and personality, anxiety and stress. It is interdisciplinary and aims to bring together different approaches for a diverse readership. Top quality papers will be accepted dealing with any aspect of affective disorders, including neuroimaging, cognitive neurosciences, genetics, molecular biology, experimental and clinical neurosciences, pharmacology, neuroimmunoendocrinology, intervention and treatment trials.