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Downregulated GPR30 Expression in the Epileptogenic Foci of Female Patients with focal cortical dysplasia type ⅱb and Tuberous Sclerosis Complex Is Correlated with 18F-FDG PET-CT Values

Downregulated GPR30 Expression in the Epileptogenic Foci of ...

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第十六届中国医师协会神经外科医师年会

作者： Zhongke Wang Kaixuan Huang Xiaolin Yang Kaifeng Shen Ling Yang Ruotong Ruan Xianjun Shi Miao Wang Gang Zhu Meihua Yang Chunqing Zhang Shengqing Lv Hui Yang Xiaotang Fan Shiyong Liu Department of Neurosurgery Xinqiao HospitalArmy Medical University (Third Military Medical University) Department of Developmental Neuropsychology School of PsychologyArmy Medical University (Third Military Medical University) Department of basic Medical College Army Medical University (Third Military Medical University)

focal cortical dysplasia type ⅱb(FCDⅡb) and tuberous sclerosis complex(TSC) are typical causes of developmental delay and refractory epilepsy.G-protein-coupled receptor 30(GPR30) is a specific estrogen receptor that is critical in neurodevelopment,neuroinflammation,and neuronal excitability,suggesting that it plays a potential role in the epilepsy of patients with FCDⅡb and TSC.Therefore,we investigated the role of GPR30 in patients with FCDⅡb and TSC.We found that the expression of GPR30 and its downstream protein kinase A(PKA) pathway were decreased and negatively correlated with seizure frequency in female patients with FCDⅡb and TSC,but not in male patients.GPR30 was widely distributed in neurons,astrocytes,and microglia,and its downregulation was especially notable in microglia.The GPR30 agonist G-1 increased the expression of PKA and p-PKA in cultured cortical neurons,and the GPR30 antagonist G-15 exhibited the opposite effects of G-1.The NF-κb signaling pathway was also activated in the specimens of female patients with FCDⅡb and TSC,and was regulated by G-1 and G-15 in cultured cortical neurons.We also found that GPR30 regulated cortical neuronal excitability by altering the frequency of spontaneous excitatory postsynaptic currents and the expression of NR2A/b.Further,the relationship between GPR30 and glycometabolism was evaluated by analyzing the correlations between GPR30 and F-FDG PET-CT values(standardized uptake values,SUVs).Positive correlations between GPR30 and SUVs were found in female patients,but not in male patients.Intriguingly,GPR30 expression and SUVs were significantly decreased in the epileptogenic tubers of female TSC patients,and ROC curves indicated that SUVs could predict the localization of epileptogenic tubers.Taken together,our results suggest a potential protective effect of GPR30 in the epileptogenesis of female patients with FCDⅡb and TSC.

关键词： G-protein-coupled receptor 30 focal cortical dysplasia type ⅱb Tuberous sclerosis complex Whole-cell patch-clamp 18F-FDG Positron emission tomography-computerized tomography Standardized uptake values

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