Abstract
It is known that neurotrophic factors are a major source of the neuroprotective effects of olfactory ensheathing cells (OECs). However, the form of neurotrophic factors that originate from OECs is not fully understood. Our previous study demonstrated that OECs could secrete exosome (OECs-Exo), which provided neuroprotection by switching the phenotype of macrophages/microglia. Considering that exosomes could also be taken up by neurons, we explored the direct effect of OECs-Exo on neuronal survival and the underlying mechanism. Electron microscopy, nano-traffic analysis, and Western blotting were applied to identify the OECs-Exo. The effect of OECs-Exo on neuronal survival was tested by flow cytometry and TUNEL staining. Western blotting and ELISA were used to detect neurotrophic factors in purified OECs-Exo. We first isolated OECs-Exo and found that OECs-Exo exerted protective effects on neuronal survival in response to TNF-α challenge. Brain-derived neurotrophic factor (BDNF) was then identified in OECs-Exo, and its receptor TrkB in neurons was activated by OECs-Exo treatment. Furthermore, we demonstrated that OECs prevented TNF-α-induced apoptosis in neurons partially through exosome-derived BDNF. Our data showed that OECs attenuated TNF-α-induced apoptosis in neurons partially through OEC-Exo-derived BDNF, which might provide a novel strategy for the neuroprotective effect of OEC-Exo-based treatment.
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The data used to support the findings of this study are available from the corresponding author upon request.
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Acknowledgements
We thank the support from Translational Medicine Center and Department of Spine Surgery of Hong Hui Hospital. We thank Xiao-Hui Wang for academic illustrating work.
Funding
This work was supported by the National Natural Science Foundation of China (NSFC, Grant number: 81830077, 81472098) to Ding-Jun Hao, NSFC (Grant number: 82071551) to Hao Yang, NSFC (Grant number: 82171471) to Hong Fan, and Shaanxi Natural Science Basic Research Program (2021JZ-39) and Shaanxi Nova Program(2022KJXX-54) to Hong Fan.
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Z.C., H.F., ZY.C., C.J., and MZ.F. contributed to conceptualization, data curation, formal analysis, investigation, and methodology. Z.C., H.F., and ZY.C. contributed to project administration, resources, software, and supervision. Z.C. and XY.G. contributed to validation and visualization. H.F., H.Y., and DJ.H. funded this work. Z.C., H. F., ZY.C., H.Y., and DJ.H. wrote, reviewed, and edited the manuscript.
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Chen, Z., Fan, H., Chen, ZY. et al. OECs Prevented Neuronal Cells from Apoptosis Partially Through Exosome-derived BDNF. J Mol Neurosci 72, 2497–2506 (2022). https://doi.org/10.1007/s12031-022-02097-5
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DOI: https://doi.org/10.1007/s12031-022-02097-5