Spatiotemporal Expression of SphK1 and S1PR2 in the Hippocampus of Pilocarpine Rat Model and the Epileptic Foci of Temporal Lobe Epilepsy.

Yuan-Yuan Dong,Min Xia,Shu-Shu Meng,Qiu-Bo Li,Lin Wang,Jun-Chen Zhang,Yan-Ke Zhang,Qing-Xia Kong,Shuai Cui

doi:10.3389/fcell.2020.00800

Abstract

Temporal lobe epilepsy (TLE) is a severe chronic neurological disease caused by abnormal discharge of neurons in the brain and seriously affect the long-term life quality of patients. Currently, new insights into the pathogenesis of TLE are urgently needed to provide more personalized and effective therapeutic strategies. Accumulating evidence suggests that sphingosine kinase 1 (SphK1)/sphingosine 1-phosphate receptor 2 (S1PR2) signaling pathway plays a pivotal role in central nervous system (CNS) diseases. However, the precise altered expression of SphK1 and S1PR2 in TLE is remaining obscure. Here, we have confirmed the expression of SphK1 and S1PR2 in the pilocarpine-induced epileptic rat hippocampus and report for the first time the expression of SphK1 and S1PR2 in the temporal cortex of TLE patients. We found an increased expression of SphK1 in the brain from both epileptic rats and TLE patients. Conversely, S1PR2 expression level was markedly decreased. We further investigated the localization of SphK1 and S1PR2 in epileptic brains. Our study showed that both SphK1 and S1PR2 co-localized with activated astrocytes and neurons. Surprisingly, we observed different subcellular localization of SphK1 and S1PR2 in epileptic brain specimens. Taken together, our study suggests that the alteration of the SphK1/S1PR2 signaling axis is closely associated with the course of TLE and provides a new target for the treatment of TLE.

Highlights

Epilepsy is a common neurological disease characterized by recurrent spontaneous epileptic seizures
The number of hippocampal astrocytes was increased 7 days post-status epilepticus (SE) and showed hypertrophy of cell bodies as mentioned previously. These findings considered together indicate that sphingosine kinase 1 (SphK1) and sphingosine 1-phosphate receptor 2 (S1PR2) were linked to a great degree with the activation of astrocyte in the epileptogenesis
We have identified the spatiotemporal expression of SphK1 and S1PR2 protein in the pilocarpine rat model and the temporal cortex specimens from patients with drug-resistant Temporal lobe epilepsy (TLE)

Summary

Introduction

Epilepsy is a common neurological disease characterized by recurrent spontaneous epileptic seizures. Temporal lobe epilepsy (TLE) is the most common pharmacoresistant epilepsy type, which accounts for 30–40% of newly diagnosed epilepsy patients (Kwan and Sander, 2004). Numerous neuropathological findings have shown that hippocampal sclerosis (HS) is a Spatiotemporal Expression of SphK1 and S1PR2 in Epilepsy representative histopathological alteration in patients with refractory epilepsy, including neuronal loss and gliosis (Lanerolle et al, 2010). Aberrant neurogenesis, and hippocampal network plasticity contributed to an epileptic focus and was considered to involve in the epileptogenesis of TLE (Mathern et al, 1996; Buckmaster and Dudek, 1997; Parent et al, 1997; Robel et al, 2015)

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