Treatment with melatonin ameliorates febrile convulsion via modulating the MEG3/miR‑223/PTEN/AKT signaling pathway

  • Authors:
    • Gefei Wu
    • Jiasheng Hu
    • Hongmin Zhu
    • Shuhua Wu
    • Sheng Huang
    • Zhisheng Liu
  • View Affiliations

  • Published online on: June 23, 2021     https://doi.org/10.3892/ijmm.2021.4987
  • Article Number: 154
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Abstract

The PTEN/AKT signaling pathway is involved in the pathogenesis of febrile convulsion (FC), a convulsion caused by abnormal electrical activity in the brain. The objective of the present study was to evaluate the therapeutic effect of melatonin (MT) on FC and the according underlying molecular mechanisms. Reverse transcription‑quantitative PCR and western blot analysis were used to explore the effects of MT on the expression levels of MEG3, microRNA (miRNA/miR)‑223, phosphatase and tensin homolog (PTEN) and protein kinase B (AKT). Luciferase assay was performed to verify the downstream targets of MEG3 and miR‑223. An animal model was established to evaluate the effects of MT on the MEG3/miR‑223/PTEN/AKT pathway. TUNEL staining was carried out to assess the effect of MT on neuronal apoptosis. Finally, the duration of seizure/convulsion was recorded to determine the effect of MT on FC. In both cell and animal models, mRNA levels of MEG3 and PTEN increased in the apoptosis group, while treatment with MT decreased the expression levels of MEG3 and PTEN. miR‑223 expression was decreased in the apoptosis group, whereas treatment with MT increased the expression level of miR‑223. Protein levels of PTEN and cleaved caspase‑3 increased in the apoptosis group, whereas treatment with MT decreased the protein level of PTEN. Phosphorylated (p)‑AKT expression was decreased in the apoptosis group and treatment with MT reversed this effect. miR‑223 could directly bind to MEG3, and PTEN was a direct target of miR‑223. MT could decrease the duration of seizure/convulsion. In all experimental groups, treatment with MT could decrease the ratio of β waves, while increasing the ratios of α, θ and δ waves. Therefore, the results from the present study collectively suggested that treatment with MT alleviated FC via the MEG3/miR‑223/PTEN/AKT pathway, which also indicated that MT could be considered as a novel strategy for the treatment of FC disease.
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August-2021
Volume 48 Issue 2

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Online ISSN:1791-244X

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Spandidos Publications style
Wu G, Hu J, Zhu H, Wu S, Huang S and Liu Z: Treatment with melatonin ameliorates febrile convulsion via modulating the MEG3/miR‑223/PTEN/AKT signaling pathway. Int J Mol Med 48: 154, 2021
APA
Wu, G., Hu, J., Zhu, H., Wu, S., Huang, S., & Liu, Z. (2021). Treatment with melatonin ameliorates febrile convulsion via modulating the MEG3/miR‑223/PTEN/AKT signaling pathway. International Journal of Molecular Medicine, 48, 154. https://doi.org/10.3892/ijmm.2021.4987
MLA
Wu, G., Hu, J., Zhu, H., Wu, S., Huang, S., Liu, Z."Treatment with melatonin ameliorates febrile convulsion via modulating the MEG3/miR‑223/PTEN/AKT signaling pathway". International Journal of Molecular Medicine 48.2 (2021): 154.
Chicago
Wu, G., Hu, J., Zhu, H., Wu, S., Huang, S., Liu, Z."Treatment with melatonin ameliorates febrile convulsion via modulating the MEG3/miR‑223/PTEN/AKT signaling pathway". International Journal of Molecular Medicine 48, no. 2 (2021): 154. https://doi.org/10.3892/ijmm.2021.4987