Glucocorticoid receptors participate in epilepsy in FCDII patients and MP model rats: A potential therapeutic target for epilepsy in patients with focal cortical dysplasia II (FCDII).

Xiaoqing Zhang, Xiaolin Yang, Bing Chen, Kaifeng Shen, Guolong Liu, Zhongke Wang, Kaixuan Huang, Gang Zhu, Tingting Wang, Shengqing Lv, Chunqing Zhang, Hui Yang, Zhi Hou, Shiyong Liu

Expert opinion on therapeutic targets 2022 Feb

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Glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs) are involved in neuronal excitability, neurogenesis, and neuroinflammation. However, the roles of GRs and MRs in epilepsy in focal cortical dysplasia II (FCDII) have not been reported. We evaluated GRs and MRs expression and distribution in FCDII patients and methylazoxymethanol-pilocarpine-induced epilepsy model rats (MP rats), and the effects of a GR agonist on neurons in human FCDII and investigated the electrophysiological properties of rats' neurons after lentivirus-mediated GR knockdown or overexpression and GR agonist or antagonist administration. GR expression (not MR) was decreased in specimens from FCDII patients and model rats. GR agonist dexamethasone reduced neuronal excitatory transmission and increased neuronal inhibitory transmission in FCDII. GR knockdown increased the excitability of cultured neurons, and GR overexpression rescued the hyperexcitability of MP-treated neurons. Moreover, dexamethasone decreased neuronal excitability and excitatory transmission in MP rats, while GR antagonist exerted the opposite effects. Dexamethasone reduced the seizure number and duration by approximately 85% and 60% in MP rats within one to two hours. These results suggested that GRs play an important role in epilepsy in FCDII and GR activation may have protective and antiepileptic effects in FCDII.

Citation

Xiaoqing Zhang, Xiaolin Yang, Bing Chen, Kaifeng Shen, Guolong Liu, Zhongke Wang, Kaixuan Huang, Gang Zhu, Tingting Wang, Shengqing Lv, Chunqing Zhang, Hui Yang, Zhi Hou, Shiyong Liu. Glucocorticoid receptors participate in epilepsy in FCDII patients and MP model rats: A potential therapeutic target for epilepsy in patients with focal cortical dysplasia II (FCDII). Expert opinion on therapeutic targets. 2022 Feb;26(2):171-186