The role of Dymeclin in chronic unpredictable mild stress-induced depression: maintaining the Golgi apparatus structure and regulating NLRP3 inflammasome activation

  • Mol Med. 2026 Jun 13. doi: 10.1186/s10020-026-01524-2.
Longfei Du  1  2 ,  Zifan Ding  3 ,  Lei Sun  4 ,  Ye Qin  5 ,  Huiling Sun  6 ,  Yuqin Pan  7 ,  Shukui Wang  8  9
Affiliations
  • 1. General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, China.
  • 2. Department of Pathology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, 225012, China.
  • 3. College of Physical Education, Yangzhou University, Yangzhou, Jiangsu, 225000, China.
  • 4. Department of Central Laboratory, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, 225012, China.
  • 5. Department of Blood Transfusion, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, 225012, China.
  • 6. General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, China. [email protected].
  • 7. General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, China. [email protected].
  • 8. General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, China. [email protected].
  • 9. Jiangsu Collaborative Innovation Center on Cancer Personalized Medicine, Nanjing Medical University, No. 101 Longmian Avenue, Jiangning District, Nanjing, Jiangsu, 211166, China. [email protected].
PMID: 42288765 DOI: 10.1186/s10020-026-01524-2
Abstract

The Golgi apparatus plays a key role in innate immune signaling, but its exact role in depression-related neuroinflammation remains unclear. The role of Dymeclin (DYM), a Golgi structural protein, in stress-related psychiatric disorders needs further clarification. This study aims to investigate whether DYM participates in the development of chronic stress-induced depression by regulating Golgi function. A mouse depression model was developed with chronic unpredictable mild stress (CUMS), followed by a rescue experiment using stereotactic injection of DYM-overexpressing lentiviruses into the hippocampus. Depression-associated behaviors, hippocampal metabolites, Golgi apparatus function, and inflammatory markers were examined using mass spectrometry, immunofluorescence, electron microscopy, and immunoprecipitation techniques. Overexpression of DYM mitigated depressive-like behaviors induced by CUMS in mice. Additionally, it enhanced the structural integrity of the Golgi apparatus, suppressed NLRP3 inflammasome activation, reduced levels of central and peripheral inflammatory factors, and partially ameliorated hippocampal metabolic disturbances. In vitro experiments further confirmed that DYM overexpression inhibited LPS-induced NLRP3 upregulation and inflammatory factor release in microglia. This study reveals that chronic stress causes depressive-like behaviors by reducing hippocampal DYM expression, leading to Golgi dysfunction and triggering NLRP3 inflammasome-related neuroinflammation and metabolic issues.This finding broadens the traditional framework of depression research, which has primarily focused on neurons and monoamine neurotransmitters, by underscoring the pivotal role of Golgi organelle homeostasis in mediating the interactions among stress, neuro-immune, and metabolic processes. Our research indicates that targeting the DYM/Golgi pathway could offer new treatment strategies and a theoretical foundation for reducing depression-related neuroinflammation and metabolic issues. Drugs targeting the structural stability of the Golgi apparatus may serve as potential candidates for novel antidepressants in the future.

Keywords
CUMS; Dymeclin; Golgi apparatus; Major depressive disorder; Metabolomics; Neuroinflammation.
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