Knockdown of GPER1 aggravates neuronal injury and cognitive dysfunction after epilepsy
- VernacularTitle:GPER1敲低加重癫痫后神经元损伤及认知功能障碍
- Author:
Shi-jie HAO
1
;
Yi-jin LUO
;
Xiao-fan REN
;
Na DING
;
Jing-bo CAO
;
Qian ZHAO
;
Wei HE
;
Shao-zhang HOU
;
Di ZUO
Author Information
- Publication Type:Journal Article
- Keywords: GPER1; epilepsy; pilocarpine; cogni-tion; neuronal apoptosis; neuroinflammation
- From: Chinese Pharmacological Bulletin 2025;41(7):1332-1339
- CountryChina
- Language:Chinese
- Abstract: Aim To investigate the impact of G pro-tein-coupled estrogen receptor 1(GPER1),also known as GPR30 playing a significant role in the nerv-ous system,on neuronal damage and cognitive dysfunc-tion following epileptic seizures.Methods The pro-tein expression levels of GPER1 and the DNA damage marker γ-H2AX in epileptic rats were assessed using Western blot.The hippocampal neuronal damage and apoptosis in pilocarpine-induced epilepsy models were evaluated using Nissl and TUNEL staining techniques,compared with GPER1 knockdown(GPER1-KD)rats with wild-type(WT)controls.The behavioral activi-ties,including memory and spatial learning,were mo-nitored during the chronic phase of epilepsy using the IntelliCage system.Results Compared to the control group,GPER1 protein expression in the cerebral cortex and hippocampus significantly increased 24 hours post-epilepsy onset.In the GPER1-KD+EP group,hipp-ocampal neuronal damage was more severe,with a sig-nificant increase in apoptotic neurons compared to the WT+EP group.The IntelliCage data revealed that during free exploration,nose contact,position learn-ing,and reverse position learning stages in the GPER1-KD+EP group exhibited fewer visits and a higher error rate than in the WT+EP group.Conclu-sions Deficiency in GPER1 impairs memory and spa-tial learning abilities following epilepsy,potentially due to exacerbated neuronal injury,apoptosis,and inflam-mation.GPER1 represents a promising therapeutic tar-get for mitigating post-epileptic nerve damage and cog-nitive impairment.
