Exosome derived from bone marrow derived mesenchymal stem cells prevents LPS-induced depressive like behaviors

Major depressive disorder (MDD) is a multifaceted mental disorder marked by a spectrum of significant and persistent low mood symptoms. Its etiology involves genetic and environmental factors. In addition, the inflammatory process plays a crucial role in the pathophysiology of depression. Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) have demonstrated significant effects in reducing proinflammatory cytokines. However, there is limited research on whether exosomes can prevent the occurrence of LPS-induced depression. This study aimed to investigate the role of BMSC-derived exosomes in LPS-induced depression and explore the underlying mechanisms. We administered exosomes to LPS-induced depression mice via the caudal vein and evaluated their effects on depressive-like behaviors. Our findings indicate that four injections of exosomes (200 µl at a concentration of 1.4 ×10 ¹¹ particles/mL, administered every three days) significantly prevented depressive-like behaviors in LPS-induced depression mice. Further analyses revealed that exosome treatment reduced levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and increased anti-inflammatory cytokine IL-10. Additionally, exosome treatment markedly reduced oxidative stress in both the central and peripheral nervous systems of LPS-treated mice. Moreover, our data suggest that exosome treatment increased astrocyte proliferation and neurogenesis in the hippocampus of LPS mice. In summary, our results demonstrate the antidepressant effects of BMSC-derived exosomes in LPS-induced depression mice, suggesting a potential new therapeutic target for major depressive disorder (MDD).