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

Jing Huang, Weijun Huang, Junzhe Yi, Yiwen Deng, Ruijie Li, Jieying Chen, Jiahao Shi, Yuan Qiu, Tao Wang, Xiaoyong Chen, Xiaoran Zhang () and Andy Peng Xiang ()
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Jing Huang: Sun Yat-Sen University
Weijun Huang: Sun Yat-Sen University
Junzhe Yi: Sun Yat-Sen University
Yiwen Deng: Jiujiang University
Ruijie Li: Sun Yat-Sen University
Jieying Chen: Sun Yat-Sen University
Jiahao Shi: Sun Yat-Sen University
Yuan Qiu: Sun Yat-Sen University
Tao Wang: Sun Yat-Sen University
Xiaoyong Chen: Sun Yat-Sen University
Xiaoran Zhang: Sun Yat-Sen University
Andy Peng Xiang: Sun Yat-Sen University

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-43150-0

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