Zhang Xian, Yang Yang, Guo Li, Zhou Jinyu, Niu Jianguo, Wang Peng, Qiang Yuanyuan, Liu Kunmei, Wen Yujun, Zhang Lianxiang, Wang Feng
Ningxia Key Laboratory of Cerebrocranial Diseases, Incubation Base of the National Key Laboratory, Ningxia Medical University, 1160 Shengli Street, Yinchuan, 750001, Ningxia, China.
School of Basic Medical Sciences, Ningxia Medical University, 1160 Shengli Street, Yinchuan, 750001, Ningxia, China.
Neurochem Res. 2021 Aug;46(8):2019-2032. doi: 10.1007/s11064-021-03336-8. Epub 2021 Jun 2.
G-protein coupled estrogen receptor 1 (GPER1) is a novel type of estrogen receptor. Several studies have shown that it has an anti-inflammatory action,which plays an important role in remyelination and cognitive ability adjustment. However, whether it is involved in the development of temporal lobe epilepsy (TLE) is still unknown. The present study established a TLE model by intraperitoneal injection of lithium chloride (3 mmol/kg) and pilocarpine (50 mg/kg) in rats to study the effect of GPER1 in the synaptic plasticity during the development of temporal lobe epilepsy. A microinjection cannula was implanted into the lateral ventricle region of rats via a stereotaxic instrument. G-1 is the specific GPER1 agonist and G15 is the specific GPER1 antagonist. The G1 or G15 and Dimethyl sulfoxide were injected into the rat brains in the intervention groups and control group, respectively. After G1 intervention, the learning and memory abilities and hippocampal neuron damage in epileptic rats were significantly improved, while G15 weakened the neuroprotective effect of GPER1. Meanwhile, G1 controlled the abnormal formation of hippocampal mossy fiber sprouting caused by seizures, and participated in the regulation of synaptic plasticity by reducing the expression of Synapsin I and increasing the expression of gephyrin. Inhibitory synapse gephyrin may play a significant role in synaptic plasticity.
G蛋白偶联雌激素受体1(GPER1)是一种新型雌激素受体。多项研究表明,它具有抗炎作用,在髓鞘再生和认知能力调节中发挥重要作用。然而,它是否参与颞叶癫痫(TLE)的发生发展仍不清楚。本研究通过腹腔注射氯化锂(3 mmol/kg)和毛果芸香碱(50 mg/kg)建立大鼠TLE模型,以研究GPER1在颞叶癫痫发生发展过程中对突触可塑性的影响。通过立体定位仪将微量注射套管植入大鼠侧脑室区域。G-1是特异性GPER1激动剂,G15是特异性GPER1拮抗剂。干预组和对照组分别将G1或G15与二甲基亚砜注入大鼠脑内。G1干预后,癫痫大鼠的学习记忆能力和海马神经元损伤明显改善,而G15削弱了GPER1的神经保护作用。同时,G1控制癫痫发作引起的海马苔藓纤维发芽异常形成,并通过降低突触素I的表达和增加gephyrin的表达参与突触可塑性的调节。抑制性突触gephyrin可能在突触可塑性中起重要作用。