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Carvacrol effectively protects demyelination by suppressing transient receptor potential melastatin 7 (TRPM7) in Schwann cells

Abstract

Peripheral neurodegenerative processes are essential for regenerating damaged peripheral nerves mechanically or genetically. Abnormal neurodegenerative processes induce peripheral neurodegenerative diseases via irreversible nerve damage. Carvacrol, a major component in Origanum vulgare, possesses various effects on organisms, such as antibiotic, anti-inflammatory and cytoprotective effects; although transient receptor potential (TRP) ankyrin 1 (TRPA1), TRP canonical 1 (TRPC1), TRP melastatin M7 (TRPM7), and TRP vanilloid 3 (TRPV3) are carvacrol-regulated TRPs, however, effect of carvacrol on the peripheral neurodegenerative process, and its underlying mechanism, remain unclear. Here, we investigated the specificity of carvacrol for TRPM7 in Schwann cells and the regulatory effect of carvacrol on TRPM7-dependent neurodegenerative processes. To construct peripheral nerve degeneration model, we used with a sciatic explant culture and sciatic nerve axotomy. Ex vivo, in vivo sciatic nerves were treated with carvacrol following an assessment of demyelination (ovoid fragmentation) and axonal degradation using morphometric indices. In these models, carvacrol effectively suppressed the morphometric indices, such as stripe, ovoid, myelin, and neurofilament indices during peripheral nerve degeneration. We found that carvacrol significantly inhibited upregulation of TRPM7 in Schwann cells. In this study, our results suggest that carvacrol effectively protects against the peripheral neurodegenerative process via TRPM7-dependent regulation in Schwann cells. Thus, pharmacological use of carvacrol could be helpful to protect against neurodegeneration that occurs with aging and peripheral neurodegenerative diseases, prophylactically.

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Acknowledgements

We thank Ms. Hyun Woo Jo (Department of Anatomy and Neurobiology, Kyung Hee University, Seoul, Korea) for her valuable discussion. This work was supported by Basic Science Research Program through National Research Foundation of Korea (NRF) Grant funded by the Korea government (MSIT) (Grant No. 2019R1F1A1048656) and a Grant from Kyung Hee University in 2019 (KHU-20191219).

Author information

YLC, MK, JJ, CP, and YH designed this study and interpreted experimental results. YLC, MK, YHK, NK, HJY, JJ, CP, and YH defined intellectual contents. YLC, MK, JJ, CP, and YH performed experiments. JJ, CP, and YH wrote the manuscript. JJ and YH obtained funds from government and Kyung Hee University. All authors read and approved the final manuscript.

Correspondence to Chan Park or Youngbuhm Huh or Junyang Jung.

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Chun, Y.L., Kim, M., Kim, Y.H. et al. Carvacrol effectively protects demyelination by suppressing transient receptor potential melastatin 7 (TRPM7) in Schwann cells. Anat Sci Int 95, 230–239 (2020). https://doi.org/10.1007/s12565-019-00514-1

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Keywords

  • Carvacrol
  • Transient receptor potential melastatin 7 (TRPM7)
  • Schwann cells
  • Demyelination
  • Axonal degradation