中国神经再生研究(英文版) ›› 2025, Vol. 20 ›› Issue (6): 1541-1554.doi: 10.4103/NRR.NRR-D-23-01878

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

外周血线粒体DNA可作为重度抑郁障碍的神经炎症生物标志物

  

  • 出版日期:2025-06-15 发布日期:2024-11-10

Peripheral mitochondrial DNA as a neuroinflammatorybiomarker for major depressive disorder

Jinmei Ye1 , Cong Duan1 , Jiaxin Han2 , Jinrong Chen2 , Ning Sun2 , Yuan Li3, *, Tifei Yuan3, 4, *, Daihui Peng1, *   

  1. 1 Division of Mood Disorder, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China;  2 Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China;  3 Shanghai Key Laboratory of Psychotic Disorders, Brain Health Institute, National Center for Mental Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; 4 Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China
  • Online:2025-06-15 Published:2024-11-10
  • Contact: Daihui Peng, PhD, pdhsh@126.com; Tifei Yuan, PhD, ytf0707@126.com; Yuan Li, PhD, zmd2012spring@126.com
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 81971269 (to DP); the Science and Technology Commission of Shanghai, No. YDZX20213100001003 (to DP).

摘要:

慢性应激下的神经炎症是重度抑郁症的发病机制之一,它阻碍了良好的预后效果和抗抑郁反应。有证据表明,线粒体DNA从中枢神经系统应激诱导的功能障碍线粒体中释放到外周血循环后,可能成为一个稳固的炎症触发器,这显示了外周血线粒体DNA可作为重度抑郁症的神经炎症生物标志物的潜力。为此,该综述旨在阐明外周血线粒体DNA如何在重度抑郁症应激诱导的神经炎症中发挥作用,并深入探讨线粒体DNA作为疾病生物标志物的潜在能力。文章对重度抑郁症的神经炎症理论进行了回顾,并提供了强有力的证据解释了外周血线粒体DNA是如何被释放的,并成为构成重度抑郁症神经炎症途径的关键生物底物。线粒体DNA被释放到线粒体外后,可被外泌体携带并运送到中枢神经系统和外周血循环的细胞外空间,这些易于检测的外泌体使包裹的线粒体DNA相对稳定。由于目前的临床可直接检测外周血中的mtDNA,这使其具备生物标志物的潜力,并为临床诊断治疗重度抑郁障碍提供价值。这些特点揭示了外周血线粒体DNA作为创新的临床生物标记物和重度抑郁症分子治疗靶点在医疗实践中的潜力。此外,文章还强调了未来将外周血线粒体DNA与其他生物标志物组合以提高诊断精确度的临床应用价值。

https://orcid.org/0000-0003-4338-967X (Daihui Peng); https://orcid.org/0000-0003-0510-715X (Tifei Yuan);

https://orcid.org/0000-0001-7735-9255 (Yuan Li)


关键词:

生物标记物, 细胞因子, 外泌体, 炎性体, 重度抑郁症, 小胶质细胞, 线粒体功能障碍, 线粒体DNA, 神经炎症, 收费样受体

Abstract: In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.

Key words: biomarker, cytokine, exosomes, inflammasome, major depressive disorder, microglia, mitochondrial DNA, mitochondrial dysfunction, neuroinflammation, Toll-like receptor