Major depression accompanied with inflammation and multiple cytokines alterations: Evidences from clinical patients to macaca fascicularis and LPS-induced depressive mice model

Yong He; Wei Li; Yue Wang; Yu Tian; Xi Chen; Zhonghao Wu; Tianlan Lan; Yan Li; Mengge Bai; Jie Liu; Ke Cheng; Peng Xie

doi:10.1016/j.jad.2020.03.131

Major depression accompanied with inflammation and multiple cytokines alterations: Evidences from clinical patients to macaca fascicularis and LPS-induced depressive mice model

J Affect Disord. 2020 Jun 15:271:262-271. doi: 10.1016/j.jad.2020.03.131. Epub 2020 Apr 25.

Authors

Yong He¹, Wei Li², Yue Wang³, Yu Tian⁴, Xi Chen⁵, Zhonghao Wu⁶, Tianlan Lan⁶, Yan Li⁴, Mengge Bai⁷, Jie Liu¹, Ke Cheng⁸, Peng Xie⁹

Affiliations

¹ Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China.
² Department of Neurology, Army medical Center of PLA, Chongqing 400042, China.
³ Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China; Institute of Neuroscience, Basic Medical College, Chongqing Medical University, Chongqing 400016, China.
⁴ Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China.
⁵ Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing 402460, China; Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China.
⁶ Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China; College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, China.
⁷ Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China; Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
⁸ Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China. Electronic address: jackchengke@163.com.
⁹ Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing 402460, China; Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China. Electronic address: xiepeng@cqmu.edu.cn.

PMID: 32479325
DOI: 10.1016/j.jad.2020.03.131

Abstract

Background: Inflammation progress has been consistently implicated in the pathophysiology of major depressive disorder (MDD). However, the underlying mechanism of inflammation and depressive symptoms still far from being fully elucidated. In addition, studies on emotional disorders could also benefit from model of the non-human primates. To explore the difference of serum multi-cytokines levels among the MDD patients and depressed macaca fascicularis as well as LPS-treated mice, thus may find the reliable potential biomarkers for MDD.

Methods: Serum multi-cytokines levels among MDD patients (n = 44) and depressed macaca fascicularis (n = 6) together with controls (n = 22 for human, n = 6 for macaques) were detected by the Bio-Plex cytokines panel. Then five of these serum cytokines in LPS-treated mice were measured via ELISA. Furthermore, these cytokines protein expressions were validated by western blotting in three depression-related regions of LPS-treated mice.

Results: Here, we found that MDD patients displayed increased concentration of 13 proinflammatory and anti-inflammatory cytokines accompanied with one decreased cytokine in peripheral serum. Meanwhile, the naturally occurring depression (NOD) macaca fascicularis merely exhibited elevated concentration of 4 peripheral cytokines (IL-6, IL-8, MCP-1, VEGF), which were in accordance with the outcomes of MDD patients. Importantly, the serum and brain tissues of LPS-treated mice also emerged similar cytokines alterations.

Conclusion: In summary, our findings strengthen the evidence that cytokines were associated with the depression, and the IL-6 and VEGF may as predictive biomarkers for novel diagnostic as well as therapeutic of depression. The hypothalamus may as a key brain region involve in the inflammatory related depressive-like behaviors.

Keywords: Cytokine; IL-6; Inflammation; LPS; Major depression disorder; VEGF.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cytokines
Depression
Depressive Disorder, Major*
Humans
Inflammation / chemically induced
Lipopolysaccharides
Macaca fascicularis
Mice

Substances

Cytokines
Lipopolysaccharides