Fyn gene silencing reduces oligodendrocytes apoptosis through inhibiting ERK1/2 phosphorylation in epilepsy

Abstract

This study aimed to investigate the effect of Fyn gene silencing on the apoptosis of oligodendrocytes (OLs) in epileptic model in vitro and the involved mechanism. Primary oligodendrocyte pro-genitor cells (OPCs) were separated from rats and differentiated to OLs. Immunofluorescent labeling showed positive expression of A2B5 in OPCs and Olig2 in OLs, suggesting the successful separation of OPCs and OLs. Three Fyn siRNAs (si-Fyn) and Fyn siRNA negative control (NC) were transfected into OLs. Western blot showed that among three si-Fyn groups, si-Fyn3 caused the lowest Fyn expression, so si-Fyn3 was chosen for following experiment. Cells were divided into four groups: Control, Model, NC and si-Fyn. In the Model group, cells were cultured in Mg-free extracellular fluid for 3 h. The morphology of control cells was normal. However, the migration of neurons, the aggregation of cell bodies and the "grid-like" changes of neural networks were observed in the model cells. OLs apoptosis in various groups was assessed by flow cytometry. Expression of Fyn, ERK1/2 and phosphorylated ERK1/2 (p-ERK1/2) in OLs of various groups was evaluated by western blot. Compared with the Control group, the apoptotic rates, the Fyn expression and p-ERK1/2/ERK1/2 ratio in the Model and NC groups increased significantly (p < .05). However, the apoptotic rate, the Fyn expression and p-ERK1/2/ERK1/2 ratio in the si-Fyn group were remarkably smaller than those in the Model group (p < .05). In conclusion, Fyn gene silencing reduced the apoptosis of OLs through inhibiting the phosphorylation of ERK1/2 in epileptic model.

Post-status epilepticus treatment with the Fyn inhibitor, saracatinib, improves cognitive function in mice

“…Fyn in neuron is known to modulate both NMDA and GABA A receptors and is associated with both excitatory and inhibitory ion channels, which are potentially associated with the onset of seizure [5,12,13]. Silencing of the Fyn gene reduced oligodendrocyte apoptosis in an epileptic model in vitro [14], and previous studies have suggested that Fyn is closely related to epilepsy. Thus, inhibiting Fyn may be a possible treatment for epilepsy.…”

Profiling Analysis of Circular RNA and mRNA in Human Temporal Lobe Epilepsy with Hippocampal Sclerosis ILAE Type 1

“…It is reported that the Fyn was upregulated in the microglia and oligodendrocytes in hippocampus during epileptogenesis. Silencing Fyn will suppress epileptogenesis through reduce neuroinflammatiom and apoptosis [30,31]. All these results indicate that SELENBP1 and GRIPAP1 in HS ILAE type 1 may affect the regeneration of neurons compared with these in no-HS type; however, this aspect of the study has not been reported yet.…”

Profiling Analysis of Circular RNA and mRNA in Human Temporal Lobe Epilepsy with Hippocampal Sclerosis ILAE Type 1

“…It is reported that the Fyn was upregulated in the microglia and oligodendrocytes in the hippocampus during epileptogenesis. Silencing Fyn will suppress epileptogenesis through reduce neuroin ammatiom and apoptosis (Sharma et al 2018;Luo et al 2020). All these results indicate that SELENBP1 and GRIPAP1 in HS ILAE type 1 may affect the regeneration of neurons compared with those in no-HS type; however, this aspect of the study has not been reported yet.…”