DUSP1 regulates hippocampal damage in epilepsy rats via ERK1/2 pathway

Abstract

Objective: To investigate the effects of DUSP1 on the hippocampal injury of young rats with epilepsy (EP) through mediating ERK1/2 signaling pathway.

Methods: Young SD rats were selected and divided into Control, EP, EP + LV-GFP, EP + LV-DUSP1, EP + LV-siDUSP1, and EP + LV-siDUSP1 + U0126 groups. Morris Water Maze Test was used to detect the spatial learning and memory. Nissl staining and TUNEL staining were conducted and the inflammatory factors and oxidative stress-related indicators were also measured. Western blotting was utilized to detect the expression of DUSP1 and ERK1/2 pathway. EP cell model was constructed in vitro to verify the in vivo results.

Results: Compared with Control group, young rats in EP group had decreased spatial learning and memory abilities and increased apoptotic rate and decreased number of Nissl positive cells. Besides, the up-regulated levels in inflammatory factors (IL-1β, IL-6), MDA content, and p-ERK1/2/ERK1/2 protein expression, as well as the down-regulated levels in DUSP1 protein expression and SOD content were also observed in EP rats. The EP rats treated with LV-DUSP1 showed obvious improvements regarding the above indicators, while those treated with LV-siDUSP1 had aggravated injury. But the effect of LV-siDUSP1 can be reversed by the treatment with ERK1/2 pathway inhibitor U0126. Further in vitro investigation verified the in vivo results.

Conclusion: DUSP1 may ameliorate the oxidative stress and inflammatory injury, as well as improve spatial learning and memory abilities via inhibiting ERK1/2 pathway, eventually playing protective roles in hippocampal injury of young rats with EP.

Keywords: DUSP1; ERK1/2 pathway; Epilepsy; Young rats.