A new mechanism of remote improvement of depression and anxiety like behavior by peripheral mesenchymal stem cells
2024-06-18
Major depressive disorder (MDD) is a serious mental illness that seriously affects the lives of patients. Selective serotonin reuptake inhibitors take several weeks to work, and more than 30% of patients are insensitive to the drug. Although ketamine and electrical stimulation have fast onset and strong therapeutic effect, there are risks of addiction, schizophrenia and epilepsy, and the promotion of therapy is limited.
Animal experiments and small sample clinical studies have preliminarily found that mesenchymal stem cells (MSC) can improve depression and anxiety-like behavior, which may be a potential method for the treatment of MDD with rapid onset and less side effects. However, intravenous infusion of MSC is mainly distributed in the lungs, and few cells can enter the brain, and the mechanism of its antidepressant effect on the regulation of central nervous system is still unknown.
Recently, studies have revealed a new mechanism of peripheral mesenchymal stem cells to remotely improve depression and anxiety-like behavior.
The researchers found that intravenous infusion of mesenchymal stem cells significantly improved depression and anxiety-like behaviors in a mouse model of chronic restraint stress (CRS) and recurrent social frustration (RSD) depression. However, the detection of inflammatory factors in the brain tissue and peripheral serum of mice showed that MSC treatment did not affect the levels of interleukin-6 (IL-6) and tumor necrosis factor-α(TNF-α), suggesting that MSC may have mechanisms other than anti-inflammatory effects.
Subsequent brain area screening revealed marked activation of dorsal raphe nucleus 5-HT neurons located in key brain areas of the central serotonergic system. Further mechanism study found that the transplanted MSC and lung rich sensory nerve fibers (VGLUT2) close, and can directly activate the vagus nerve sensory fibers, through the lung vagus-solitary nucleus-dorsal raphe nucleus pathway to the central transmission of signals.
In addition, the researchers also showed that brain-derived neurotrophic factor (BDNF) secreted by MSC plays an important role in the activation of pulmonary nerve fibers, and direct physical inhalation of BDNF receptor agonist (7,8-DHF) can significantly improve depression and anxiety-like behavior in mice.
In summary, this study reveals that MSC plays an antidepressant and anxiety role through the lung vagus-solitary-dorsal raphe nucleus pathway, which provides a new therapeutic target for the treatment of depression.
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