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Updated: Mar 14, 2026
High Throughput Characterization of Adult Stem Cells Engineered for Delivery of Therapeutic Factors for Neuroprotective Strategies
Published on: January 4, 2015
Bone marrow mesenchymal stem cells attenuate 2,5-hexanedione-induced neuronal apoptosis through a NGF/AKT-dependent
Qingshan Wang1, Guohua Sun2, Chenxue Gao1
1Department of Occupational and Environmental Health, Dalian Medical University, Dalian, Liaoning 116044, China.
Abstract:
Growing evidence suggests that the increased neuronal apoptosis is involved in n-hexane-induced neuropathy. We have recently reported that bone marrow-mesenchymal stem cells-derived conditioned medium (BMSC-CM) attenuated 2,5-hexanedione (HD, the active metabolite of n-hexane)-induced apoptosis in PC12 cells. Here, we explored the anti-apoptotic efficacy of BMSC in vivo. HD-treated rats received BMSC by tail vein injection 5 weeks after HD intoxication. We found that in grafted rats, BMSC significantly attenuated HD-induced neuronal apoptosis in the spinal cord, which was associated with elevation of nerve growth factor (NGF). Neutralization of NGF in BMSC-CM blocked the protection against HD-induced apoptosis in VSC4.1 cells, suggesting that NGF is essential for BMSC-afforded anti-apoptosis. Mechanistically, we found that the decreased activation of Akt induced by HD was significantly recovered in the spinal cord by BMSC and in VSC4.1 cells by BMSC-CM in a TrkA-dependent manner, leading to dissociation of Bad/Bcl-xL complex in mitochondria and release of anti-apoptotic Bcl-xL. The importance of Akt was further corroborated by showing the reduced anti-apoptotic potency of BMSC in HD-intoxicated VSC4.1 cells in the presence of Akt inhibitor, MK-2206. Thus, our findings show that BMSC attenuated HD-induced neuronal apoptosis in vivo through a NGF/Akt-dependent manner, providing a novel solution against n-hexane-induced neurotoxicity.
Insights
Bone marrow-derived stem cells (BMSC) reduce n-hexane toxicity by preventing nerve cell death. This neuroprotective effect involves nerve growth factor (NGF) and Akt signaling pathways, offering a potential treatment for neuropathy.
Area of Science:
- Neuroscience
- Stem Cell Biology
- Toxicology
Background:
- n-Hexane neuropathy is linked to increased neuronal apoptosis.
- Bone marrow-mesenchymal stem cells-derived conditioned medium (BMSC-CM) previously showed anti-apoptotic effects on PC12 cells exposed to 2,5-hexanedione (HD).
Purpose of the Study:
- To investigate the in vivo anti-apoptotic efficacy of bone marrow-mesenchymal stem cells (BMSC) against n-hexane-induced neurotoxicity.
- To elucidate the underlying mechanisms, including the roles of nerve growth factor (NGF) and the Akt signaling pathway.
Main Methods:
- HD-treated rats received BMSC via tail vein injection.
- BMSC-CM was used to treat VSC4.1 cells exposed to HD.
- NGF neutralization and Akt inhibition (MK-2206) were employed to assess pathway involvement.
- Western blotting and mitochondrial assays were used to analyze protein activation and complex dissociation.
Main Results:
- BMSC transplantation significantly attenuated HD-induced neuronal apoptosis in the spinal cords of rats.
- This neuroprotection was associated with elevated NGF levels.
- NGF neutralization blocked BMSC-CM's protective effect in VSC4.1 cells.
- BMSC and BMSC-CM treatment recovered HD-induced decrease in Akt activation in a TrkA-dependent manner.
- Akt inhibition reduced the anti-apoptotic potency of BMSC.
Conclusions:
- BMSC effectively attenuates n-hexane-induced neuronal apoptosis in vivo.
- The neuroprotective mechanism involves NGF and the Akt signaling pathway.
- BMSC represents a promising therapeutic strategy for n-hexane-induced neurotoxicity.
