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Published on: October 21, 2014
Ghrelin inhibits oligodendrocyte cell death by attenuating microglial activation
Jee Youn Lee1, Tae Young Yune2
1Age-Related and Brain Diseases Research Center, Kyung Hee University School of Medicine, Seoul, Korea.
Background:
Recently, we reported the antiapoptotic effect of ghrelin in spinal cord injury-induced apoptotic cell death of oligodendrocytes. However, how ghrelin inhibits oligodendrocytes apoptosis, is still unknown. Therefore, in the present study, we examined whether ghrelin inhibits microglia activation and thereby inhibits oligodendrocyte apoptosis.
Methods:
Using total cell extracts prepared from BV-2 cells activated by lipopolysaccharide (LPS) with or without ghrelin, the levels of p-p38 phosphor-p38 mitogen-activated protein kinase (p-p38MAPK), phospho-c-Jun N-terminal kinase (pJNK), p-c-Jun, and pro-nerve growth factor (proNGF) were examined by Western blot analysis. Reactive oxygen species (ROS) production was investigated by using dichlorodihydrofluorescein diacetate. To examine the effect of ghrelin on oligodendrocyte cell death, oligodendrocytes were cocultured in transwell chambers of 24-well plates with LPS-stimulated BV-2 cells. After 48 hours incubation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and terminal deoxynucleotidyl transferase 2'-deoxyuridine, 5'-triphosphate nick end labeling staining were assessed.
Results:
Ghrelin treatment significantly decreased levels of p-p38MAPK, p-JNK, p-c-Jun, and proNGF in LPS-stimulated BV-2 cells. ROS production increased in LPS-stimulated BV-2 cells was also significantly inhibited by ghrelin treatment. In addition, ghrelin significantly inhibited oligodendrocyte cell death when cocultured with LPS-stimulated BV-2 cells.
Conclusion:
Ghrelin inhibits oligodendrocyte cell death by decreasing proNGF and ROS production as well as p38MAPK and JNK activation in activated microglia as an anti-inflammatory hormone.
Insights
Ghrelin reduces oligodendrocyte cell death by inhibiting microglia activation. This neuroprotective effect involves decreasing pro-nerve growth factor and reactive oxygen species, and suppressing inflammatory signaling pathways.
Area of Science:
- Neuroscience
- Cell Biology
- Immunology
Background:
- Ghrelin demonstrates antiapoptotic effects in spinal cord injury models.
- The precise mechanism by which ghrelin protects oligodendrocytes remains unclear.
- This study investigates ghrelin's role in modulating microglia activation to prevent oligodendrocyte apoptosis.
Purpose of the Study:
- To determine if ghrelin inhibits microglia activation.
- To elucidate the molecular pathways involved in ghrelin's neuroprotective effects.
- To assess ghrelin's impact on oligodendrocyte survival in an inflammatory context.
Main Methods:
- Western blot analysis of p38MAPK, JNK, c-Jun, and proNGF in LPS-stimulated BV-2 microglia with or without ghrelin.
- Measurement of reactive oxygen species (ROS) production using dichlorodihydrofluorescein diacetate.
- Co-culture of oligodendrocytes with LPS-stimulated BV-2 cells to evaluate cell death via MTT assay and TUNEL staining.
Main Results:
- Ghrelin significantly reduced levels of p-p38MAPK, p-JNK, p-c-Jun, and proNGF in activated microglia.
- Ghrelin treatment inhibited lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) production.
- Ghrelin significantly protected oligodendrocytes from cell death when co-cultured with activated microglia.
Conclusions:
- Ghrelin acts as an anti-inflammatory hormone by inhibiting microglia activation.
- Ghrelin protects oligodendrocytes by reducing proNGF and ROS production.
- Ghrelin's mechanism involves suppressing p38MAPK and JNK signaling pathways in activated microglia.
