Journal
EPILEPSY RESEARCH
Volume 182, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.eplepsyres.2022.106915
Keywords
Dynamin 1; Phosphorylation; ADBE; Epileptic seizure
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The study revealed that dephospho-dynamin 1 triggers activity-dependent bulk endocytosis (ADBE) to meet the requirements of high-frequency discharges during epileptic seizures.
Background and purpose: Epilepsy is a severe neurological and mental disorder, and not all patients adequately respond to the current treatments. Dynamin 1 plays a key role in synaptic endocytosis and the modulation of neurological function.Material and methods: Cultured hippocampal neurons were used in the study. First, the viability of neurons was determined by the CCK-8 assay after culturing in magnesium-free medium, DMSO, dynasore (dynamin agonist), and PIP2 (dynamin antagonist). Then, the effect of dynasore on seizure activity was evaluated. Next, we tested the levels of phospho-dynamin 1/total dynamin 1 and dynamin 1 mRNA in the control group and four epilepsy groups. Moreover, the uptake of tetramethylrhodamine-dextran in the different groups was measured.Results: Dephospho-dynamin 1 expression was significantly increased in hyperexcitable neurons, while there was no change in total dynamin 1 level. The level of dephospho-dynamin 1 in hyperexcitable neurons was reduced when cultured with dynasore but increased with PIP2 treatment. Activity-dependent bulk endocytosis (ADBE) was upregulated in hyperexcitable neurons. Along with a decrease in dephospho-dynamin 1 level, ADBE was also downregulated with dynasore treatment, while PIP2 did not affect ABDE. The close link between the dephosphorylation status of dynamin 1 and ADBE suggests that ADBE activation depends on dynamin 1 dephosphorylation. Conclusion: Dephospho-dynamin 1 triggers ADBE to meet the requirements of high-frequency discharges during epileptic seizures.
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