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Related Experiment Video

Updated: May 22, 2025

Animal Models of Depression - Chronic Despair Model CDM
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Inflammation molecular network alterations in a depressive-like primate model.

Siyuan Bu1, Qingyun Wang2, Gaojia Zhang3

  • 1Department of Neurology in Affiliated ZhongDa Hospital and Jiangsu Provincial Medical Key Discipline, School of Medicine, Institution of Neuropsychiatry, Key Laboratory of Developmental Genes and Human Disease of Ministry of Education, Southeast University, Nanjing, Jiangsu 210009, China.

Journal of Affective Disorders
|March 13, 2025
PubMed
Summary

Major Depressive Disorder (MDD) lacks clear biomarkers. This study identifies neurocan (NCAN) and Toll-like receptor 4 (TLR4) network molecules as potential biomarkers for MDD, linked to neuroinflammation.

Keywords:
BiomarkerCerebrospinal fluidDepressionInflammation molecular networkMacaca fascicularisTLR4

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Area of Science:

  • Neuroscience
  • Immunology
  • Biomarker Discovery

Background:

  • Major Depressive Disorder (MDD) lacks definitive diagnostic biomarkers.
  • Neuroinflammation is implicated in depression pathogenesis, suggesting inflammatory factors as potential biomarkers.
  • Non-human primates display depression-like behaviors under chronic stress, serving as a relevant model.

Purpose of the Study:

  • To screen for potential biological markers of depression using a non-human primate model.
  • To identify neuroinflammatory molecules associated with depression-like states.
  • To validate findings across species using human patient data.

Main Methods:

  • Whole transcriptome sequencing of peripheral blood in depressive-like (DL) cynomolgus monkeys and controls.
  • Olink proximity extension assay to measure plasma and cerebrospinal fluid neurology-related and inflammatory molecules.
  • Cross-species validation using postmortem brain tissue and peripheral blood RNA sequencing data from MDD patients (GEO database).

Main Results:

  • Depressive-like monkeys showed elevated neurocan (NCAN) levels compared to controls.
  • RNA sequencing identified Toll-like receptor 4 (TLR4) and S100 calcium-binding proteins as key inflammatory network molecules.
  • Human MDD patient data revealed up-regulation of S100A8 and S100A9 in the anterior cingulate cortex.

Conclusions:

  • Depressive-like monkeys exhibit a state of chronic low-grade inflammation.
  • Neurocan (NCAN) and the TLR4 inflammatory network are identified as potential biomarkers for MDD.
  • Findings suggest conserved neuroinflammatory pathways in depression across species.