Abstract

Epilepsy is a common chronic neurological disorder worldwide. To investigate the effects of miR-21-5p and signal transducer and activator of transcription-3 (STAT3) expressions on the apoptosis of hippocampal neurons in epileptic rats. We created a rat model of epilepsy and examined the relationship between miR-21-5p and STAT3 using a bioinformatics website and dual the luciferase reporter (DLR) assay. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blot were used to detect the expression levels of miR-21-5p and STAT3 in hippocampal neurons as well as the protein expression levels of cleaved caspase-3, Bax and Bcl-2, which were related to apoptosis of hippocampal neuron. The apoptosis and survival of hippocampal neurons were detected using TUNEL and Nissl staining. Expressions of inflammatory factors interleukin (IL)-6 and tumor necrosis factor α (TNF-α) in serum were examined with enzyme-linked immunosorbent assay (ELISA). miR-21-5p can bind to STAT3. Compared with the miR-21-5p inhibitor negative control (NC) group, the expression levels of caspase-3 and Bax were higher and the expression level of Bcl-2 was lower in the miR-21-5p inhibitor group, whereas the caspase-3 and Bax levels were lower and Bcl-2 level was higher in the si-STAT3 (interfering STAT3 gene expression by transfecting small interfering RNA) group (all p < 0.05). Treatment with miR-21-5p inhibitor can lead to significant loss and apoptosis of hippocampal neurons, while interfering with STAT3 expression can reduce the loss and apoptosis of the neurons (all p < 0.05). Compared with the miR-21-5p inhibitor NC group, the level of IL-6 was lower in the si-STAT3 group and higher in the miR-21-5p inhibitor group (both p < 0.05). miR-21-5p can inhibit STAT3 expression and reduce apoptosis and loss of hippocampal neurons and IL-6 level, thereby achieving protective effects on hippocampal neurons of epileptic rats.

Highlights

  • Epilepsy is a common chronic neurological disorder worldwide

  • Compared with the miR-21-5p inhibitor negative control (NC) group, the expression levels of caspase-3 and Bax were higher and the expression level of Bcl-2 was lower in the miR-21-5p inhibitor group, whereas the caspase-3 and Bax levels were lower and Bcl-2 level was higher in the si-signal transducer and activator of transcription-3 (STAT3) group

  • Treatment with miR-21-5p inhibitor can lead to significant loss and apoptosis of hippocampal neurons, while interfering with STAT3 expression can reduce the loss and apoptosis of the neurons

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Summary

Introduction

Epilepsy is a common chronic neurological disorder worldwide It is characterized by recurrent unpredictable seizures and often results from overstimulation of neurons or disorders of metabolism and the nervous system due to brain damage.[1–3]. According to the statistics from the World Health Organization (WHO) on the worldwide prevalence rate of diseases in 2010, epilepsy ranked second among neurological diseases.[4]. The lifespan of patients with epilepsy is much shorter than of healthy people.[5]. Even though the treatment for epilepsy, including medication, neuromodulation, surgical management, and diet control, have been advancing in recent years, nearly 30% of the patients still do not respond to epilepsy medications and experience regular onset after treatment.[6,7].

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