2. Academic Validation
  3. Mesenchymal stromal cells alleviate depressive and anxiety-like behaviors via a lung vagal-to-brain axis in male mice

Mesenchymal stromal cells alleviate depressive and anxiety-like behaviors via a lung vagal-to-brain axis in male mice

  • Nat Commun. 2023 Nov 16;14(1):7406. doi: 10.1038/s41467-023-43150-0.
Jing Huang # 1 2,  Weijun Huang # 1 2,  Junzhe Yi # 1 2,  Yiwen Deng 3,  Ruijie Li 1 2,  Jieying Chen 1 2,  Jiahao Shi 1 2,  Yuan Qiu 1 2 4,  Tao Wang 1 2 4,  Xiaoyong Chen 1 2 4,  Xiaoran Zhang 5 6 7,  Andy Peng Xiang 8 9 10
Affiliations

Affiliations

  • 1 Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China.
  • 2 National-Local Joint Engineering Research Center for Stem Cells and Regenerative Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China.
  • 3 Key Laboratory of Medical Transformation of Jiujiang, Jiujiang University, Jiujiang, Jiangxi, 332005, China.
  • 4 Department of Histoembryology and Cell Biology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China.
  • 5 Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China. zhangxr53@mail.sysu.edu.cn.
  • 6 National-Local Joint Engineering Research Center for Stem Cells and Regenerative Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China. zhangxr53@mail.sysu.edu.cn.
  • 7 Department of Histoembryology and Cell Biology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China. zhangxr53@mail.sysu.edu.cn.
  • 8 Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China. xiangp@mail.sysu.edu.cn.
  • 9 National-Local Joint Engineering Research Center for Stem Cells and Regenerative Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China. xiangp@mail.sysu.edu.cn.
  • 10 Department of Histoembryology and Cell Biology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China. xiangp@mail.sysu.edu.cn.
  • # Contributed equally.
PMID: 37973914 DOI: 10.1038/s41467-023-43150-0
Abstract

Major depressive disorder (MDD) is one of the most common and disabling mental disorders, and current strategies remain inadequate. Although mesenchymal stromal cells (MSCs) have shown beneficial effects in experimental models of depression, underlying mechanisms remain elusive. Here, using murine depression models, we demonstrated that MSCs could alleviate depressive and anxiety-like behaviors not due to a reduction in proinflammatory cytokines, but rather activation of dorsal raphe nucleus (DRN) 5-hydroxytryptamine (5-HT) neurons. Mechanistically, peripheral delivery of MSCs activated pulmonary innervating vagal sensory neurons, which projected to the nucleus tractus solitarius, inducing the release of 5-HT in DRN. Furthermore, MSC-secreted brain-derived neurotrophic factor activated lung sensory neurons through tropomyosin receptor kinase B (TrkB), and inhalation of a TrkB Agonist also achieved significant therapeutic effects in male mice. This study reveals a role of peripheral MSCs in regulating central nervous system function and demonstrates a potential "lung vagal-to-brain axis" strategy for MDD.

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