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A Behavioral Screen for Heat-Induced Seizures in Mouse Models of Epilepsy
Published on: July 12, 2021
Treatment with melatonin ameliorates febrile convulsion via modulating the MEG3/miR‑223/PTEN/AKT signaling pathway
Gefei Wu1, Jiasheng Hu1, Hongmin Zhu1
1Neurology Department, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430016, P.R. China.
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.
Insights
Melatonin (MT) alleviates febrile convulsions (FC) by modulating the MEG3/microRNA-223/PTEN/AKT pathway. This study suggests MT as a potential novel therapeutic strategy for FC.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- The PTEN/AKT signaling pathway is implicated in the pathogenesis of febrile convulsions (FC).
- Understanding the molecular mechanisms underlying FC is crucial for developing effective treatments.
Purpose of the Study:
- To evaluate the therapeutic potential of melatonin (MT) in febrile convulsions (FC).
- To elucidate the underlying molecular mechanisms of MT's action on the MEG3/miR-223/PTEN/AKT pathway in FC.
Main Methods:
- Utilized reverse transcription-quantitative PCR and Western blot to analyze gene and protein expression.
- Employed luciferase assays to confirm downstream targets of MEG3 and miR-223.
- Established cell and animal models of FC, incorporating TUNEL staining and seizure duration recording.
Main Results:
- MT treatment decreased MEG3 and PTEN mRNA levels while increasing miR-223 expression in FC models.
- MT reduced PTEN and cleaved caspase-3 protein levels, and reversed the decrease in phosphorylated AKT.
- MT treatment shortened seizure duration and altered EEG wave ratios (decreased β, increased α, θ, δ).
Conclusions:
- Melatonin effectively alleviates febrile convulsions (FC) by regulating the MEG3/miR-223/PTEN/AKT signaling pathway.
- MT demonstrates potential as a novel therapeutic strategy for managing FC.
- The findings provide insights into the neuroprotective effects of melatonin in FC.
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