MicroRNA-187 inhibits pentylenetetrazol-induced neuronal apoptosis and alleviates development of epilepsy in epileptic rats by regulating SPRY1 expression

Abstract

Purpose: To explore the role of microRNA-187 on the pathological process of epilepsy. Methods: The seizure score of epileptic rats was evaluated according to Racine’s scale. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to determine the expression levels of microRNA-187 (miR-187). Western blot technique was conducted to assess the expression levels of caspase 3, B-cell lymphoma-2 (BCL-2), and poly (ADP-ribose) polymerase (PARP)] and activation of phosphatase and tensin homolog (PTEN)/PI3K/AKT cascade. Caspase 3 colorimetric assay kit was employed to evaluate the activity of caspase 3. Dual-luciferase reporter gene system was used to explore the regulating mechanisms of miR-187 and protein sprouty homolog 1 gene (SPRY1). Results: The results showed that miR-187 was aberrantly downregulated in the hippocampus regions of pentylenetetrazol (PTZ)-treated rats compared to normal rats (p < 0.05). Furthermore, PTZ promoted caspase 3-dependent neuronal apoptosis by increasing the expression of pro-apoptosis protein PARP and decreasing the expression levels of BCL-2 in rats. On the other hand, overexpression of miR-187 downregulated SPRY1 as well as PTEN (p < 0.05), thereby activating the downstream PI3K/AKT signaling pathway. Notably, the effects of upregulated miR-187 on neuronal apoptosis and epilepsy development in PTZ-induced rats was reversed by the concomitant overexpression of SPRY1 (p < 0.05). Conclusion: The results of this research show that overexpressed miR-187 alleviates the development of PTZ-induced neuronal apoptosis and epilepsy in epileptic rat models by regulating SPRY1 expression. These findings can hopefully be beneficial for the discovery of new therapeutic strategies for epilepsy treatment.