No abstract

Epilepsy is a clinical syndrome caused by the highly synchronized abnormal discharge of brain neurons. It has the characteristics of paroxysmal, transient, repetitive, and stereotyped. Circular RNAs (circRNAs) are a recently discovered type of noncoding RNA with diverse cellular functions related to their excellent stability; additionally, some circRNAs can bind and regulate microRNAs (miRNAs). The present study was designed to screen the differentially expressed circRNA in an acute seizure model of epilepsy in mice, analyze the related miRNA and mRNA, and study their participating functions and enrichment pathways. In order to obtain the differential expression of circRNA in epilepsy and infer their function, we used next-generation sequencing and found significantly different transcripts. CIRI (circRNA identifier) software was used to predict circRNA from the hippocampus cDNA, EdgeR was applied for the differential circRNA analysis between samples, and Cytoscape 3.7.2 software was used to draw the network diagram. A total of 10,388 differentially expressed circRNAs were identified, of which 34 were upregulated and 66 were downregulated. Among them, mm9_circ_008777 and mm9_circ_004424 were the key upregulated genes, and their expression in the epilepsy group was verified using Quantitative real-time PCR (QPCR). The analysis indicated that the extracted gene ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways were closely related to several epilepsy-associated processes. This study determined that mm9_circ_008777 and mm9_circ_004424 are potential biomarkers of epilepsy, which play important roles in epilepsy-related pathways. These results could help improve the understanding of the biological mechanisms of circRNAs and epilepsy treatments.

Temporal lobe epilepsy (TLE) is a chronic disease of the nervous system, associated with increased proliferation in the hippocampus. Urothcarcinoma associated 1 (UCA1) is a long long non-coding RNA that was shown to regulate proliferation and differentiation of neural progenitors in vitro. We hypothesised that TLE-associated abnormal proliferation is a consequence of the downregulation of UCA1. This hypothesis was tested in mice with kainic acid (KA)-induced seizures, and then the potential mechanism was explored in vitro and in vivo. Result showed that the expression of UCA1 and Secreted Frizzled Related Protein 1 (SFRP1) were significantly reduced in hippocampal tissues of epileptic mice, while miR-375 was increased compared with the control group. Pearson correlation analysis showed that UCA1 was positively correlated with SFRP1, while miR-375 was negatively correlated with UCA1 and SFRP1. Besides, UCA1 was overexpressed in mice and the overexpression of UCA1 significantly reversed the abnormal proliferation of hippocampal neurons in epilepsy mice. In vitro Luciferase assay showed that UCA1 and Sfrp1 are both the targets of miR-375, and UCA1 promotes the expression of Sfrp1 by competitively adsorbing miR-375, thereby inhibiting the activation of the WNT/β-catenin pathway. The inactivation of the WNT/β-catenin pathway prevented the abnormal proliferation of neural progenitors in the epileptic hippocampus. In conclusion, our findings provide a theoretical basis for the clinical application of UCA1.

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.