Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.
Clinical Laboratory, Affiliated Hospital of West Anhui Health Vocational College, Lu'an, Anhui, People's Republic of China.
Int J Nanomedicine. 2024 Sep 2;19:8971-8985. doi: 10.2147/IJN.S477482. eCollection 2024.
To investigate the neuroplasticity hypothesis of depression by measuring brain-derived neurotrophic factor (BDNF) levels in plasma astrocyte-derived extracellular vesicles (ADEVs) and to evaluate their potential as biomarkers for depression compared with plasma BDNF levels.
Thirty-five patients with major depressive disorder (MDD) and 35 matched healthy controls (HCs) were enrolled. Plasma ADEVs were isolated using a combination of ultracentrifugation and immunoaffinity capture. Isolated ADEVs were validated using transmission electron microscopy, nanoparticle tracking analysis, and Western blotting. BDNF levels were quantified in both ADEVs and plasma. ALG-2-interacting protein X (Alix) and cluster of differentiation 81 (CD81) levels, two established extracellular vesicle markers, were measured in ADEVs.
After false discovery rate correction, patients with MDD exhibited higher CD81 levels ( = 0.040) and lower BDNF levels ( = 0.043) in ADEVs than HCs at baseline. BDNF levels in ADEVs normalized to CD81 ( = 0.002) and Alix ( = 0.040) remained consistent with this finding. Following four weeks of selective serotonin reuptake inhibitor treatment (n=10), CD81 levels in ADEVs decreased ( = 0.046), while BDNF levels normalized to CD81 increased ( = 0.022). BDNF levels in ADEVs were more stable than in plasma. Exploratory analysis revealed no correlation between BDNF levels in ADEVs and plasma (=0.117, = 0.334).
This study provides human in vivo evidence supporting the neuroplasticity hypothesis of depression by demonstrating altered BDNF levels in ADEVs. ADEVs may be more suitable for developing biomarkers of depression than plasma-derived biomarkers.
通过测量血浆星形细胞衍生细胞外囊泡（ADEVs）中的脑源性神经营养因子（BDNF）水平，来探究抑郁症的神经可塑性假说，并评估其作为抑郁症生物标志物的潜力，与血浆 BDNF 水平相比。
共纳入 35 名患有重度抑郁症（MDD）的患者和 35 名匹配的健康对照者（HCs）。使用超速离心和免疫亲和捕获相结合的方法分离血浆 ADEVs。使用透射电子显微镜、纳米颗粒跟踪分析和 Western blot 验证分离的 ADEVs。定量检测 ADEVs 和血浆中的 BDNF 水平。在 ADEVs 中测量 ALG-2 相互作用蛋白 X（Alix）和 CD81 两种公认的细胞外囊泡标志物的水平。
在经过错误发现率校正后，与 HCs 相比，MDD 患者的 ADEVs 中 CD81 水平更高（ = 0.040），BDNF 水平更低（ = 0.043）。ADEVs 中 BDNF 水平与 CD81（ = 0.002）和 Alix（ = 0.040）的标准化比值仍与这一发现一致。在接受选择性 5-羟色胺再摄取抑制剂治疗（n=10）四周后，ADEVs 中的 CD81 水平下降（ = 0.046），而标准化至 CD81 的 BDNF 水平增加（ = 0.022）。ADEVs 中的 BDNF 水平比血浆中的更稳定。探索性分析显示，ADEVs 中的 BDNF 水平与血浆中 BDNF 水平无相关性（ = 0.117， = 0.334）。
本研究提供了人类体内证据，通过证明 ADEVs 中 BDNF 水平改变，支持了抑郁症的神经可塑性假说。与血浆衍生的生物标志物相比，ADEVs 可能更适合开发抑郁症的生物标志物。
