Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

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

Limei Diao^1,2, Haichun Yu³, Shungui Wang⁴, Qian Yu⁴, Huaxia Li⁴, Ling Lu⁴, Xianqiu Liao⁴, Huan Li⁴, Xiaoqiang Qiu¹

¹Department of School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021; ²Department of Neurology, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, Guangxi 530023; ³Department of Numerical Control Technology, Guangxi Technological College of Machinery and Electricity, Nanning, Guangxi 530007; ⁴Department of Neurology, Graduate School of Guangxi University of Chinese Medicine, Nanning, Guangxi 530023, China.

For correspondence:- Xiaoqiang Qiu Email: QiuXQiangcbn@163.com Tel:+867715350823

Accepted: 25 August 2019 Published: 30 September 2019

Citation: Diao L, Yu H, Wang S, Yu Q, Li H, Lu L, et al. MicroRNA-187 inhibits pentylenetetrazol-induced neuronal apoptosis and alleviates development of epilepsy in epileptic rats by regulating SPRY1 expression. Trop J Pharm Res 2019; 18(9):1823-1829 doi: 10.4314/tjpr.v18i9.6

© 2019 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

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.

Keywords: Epilepsy, Neuronal apoptosis, miR-187, SPRY1