The Neuroprotective Effects of BMSC-Derived Exosomes against Glutamate-Induced HT22 Cell Cytotoxicity

• Published in: Neuroscience 2024-03, Vol.542, p.1-10
• Main Authors: Rong, Jingtong, Sun, Siqi, Xu, Shu-xian, Xie, Xin-hui, Wang, Chao, Chen, Guopeng, Kang, Lijun, Xiang, Dan, Liu, Zhongchun
• Format: Article
• Language: English
• Subjects: Animals; apoptosis; exosomes; Exosomes - metabolism; Glutamic Acid - metabolism; Glutamic Acid - toxicity; mesenchymal stem cell; Mice; MicroRNAs - metabolism; Neuroprotective Agents - metabolism; Neuroprotective Agents - pharmacology; neuroprotective effects; neurotoxicity; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins c-akt - metabolism; TOR Serine-Threonine Kinases - metabolism
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2024.01.023

•BMSC-Exos can protect neurons from excitotoxicity induced by glutamate.•The neuroprotective effect of BMSC-Exos is achieved by alleviating neuronal apoptosis.•BMSC-Exos alleviate neuronal apoptosis via PI3K/Akt/mTOR signaling. Many central nervous system diseases are closely related to nerve damage caused by dysregulation of the endogenous neurotransmitter glutamate. Exosomes derived from bone marrow mesenchymal stem cells (BMSC-Exos) play an important role in improving injury and regeneration functions. However, its mechanism remains unknown. Therefore, the aim of this study is to investigate whether and how BMSC-Exos improve neurotoxicity caused by glutamate and to fill the gap in the literature. In this study, glutamate-treated HT22 cells were first exposed to mouse-derived BMSC-Exos at different concentrations to observe their effects on HT22 apoptosis. Next, we treated glutamate-treated HT22 cells with mouse-derived BMSC-Exos. We then inhibited the PI3K/Akt/mTOR signaling pathways using the PI3K/Akt inhibitor and the mTOR inhibitor, respectively, and observed the protective effect of mouse-derived BMSC-Exos on HT22 cells treated with glutamate. Our results show that BMSC-Exos reduced apoptosis triggered by glutamate stimulation, increased cell vitality, and decreased the levels of proapoptotic proteins while increasing the levels of anti-apoptotic proteins. The protective effect of BMSC-Exos was weakened when PI3K/Akt inhibitor and mTOR inhibitor were added. To sum up, we draw the following conclusions: BMSC-Exos can reduce neuronal apoptosis and apoptosis-related protein expression after glutamate stimulation by regulating the PI3K/Akt/mTOR signaling pathway.