Dong Yuan-Yuan, Xia Min, Wang Lin, Cui Shuai, Li Qiu-Bo, Zhang Jun-Chen, Meng Shu-Shu, Zhang Yan-Ke, Kong Qing-Xia
Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, China.
Department of Surgery, Weifang Medical University, Weifang, China.
Front Cell Dev Biol. 2020 Oct 8;8:800. doi: 10.3389/fcell.2020.00800. eCollection 2020.
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.
颞叶癫痫(TLE)是一种由大脑神经元异常放电引起的严重慢性神经疾病,严重影响患者的长期生活质量。目前,迫切需要对TLE的发病机制有新的见解,以提供更个性化和有效的治疗策略。越来越多的证据表明,鞘氨醇激酶1(SphK1)/1-磷酸鞘氨醇受体2(S1PR2)信号通路在中枢神经系统(CNS)疾病中起关键作用。然而,SphK1和S1PR2在TLE中的确切表达变化仍不清楚。在此,我们证实了SphK1和S1PR2在毛果芸香碱诱导的癫痫大鼠海马中的表达,并首次报道了SphK1和S1PR2在TLE患者颞叶皮质中的表达。我们发现癫痫大鼠和TLE患者大脑中SphK1的表达均增加。相反,S1PR2的表达水平明显降低。我们进一步研究了SphK1和S1PR2在癫痫大脑中的定位。我们的研究表明,SphK1和S1PR2均与活化的星形胶质细胞和神经元共定位。令人惊讶的是,我们在癫痫脑标本中观察到SphK1和S1PR2的亚细胞定位不同。综上所述,我们的研究表明SphK1/S1PR2信号轴的改变与TLE的病程密切相关,并为TLE的治疗提供了新的靶点。