1. 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
- Author
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Mei-Hua Yang, Zhongke Wang, Kaixuan Huang, Ruotong Ruan, Xianjun Shi, Kaifeng Shen, Shi-Yong Liu, Miao Wang, Gang Zhu, Xiaolin Yang, Ling Yang, Sheng-Qing Lv, Xiaotang Fan, Chun-Qing Zhang, and Hui Yang
- Subjects
0301 basic medicine ,Male ,tuberous sclerosis complex ,Epileptogenesis ,Receptors, G-Protein-Coupled ,Tuberous sclerosis ,Epilepsy ,Mice ,0302 clinical medicine ,Tuberous Sclerosis ,Positron Emission Tomography Computed Tomography ,Receptor ,Child ,whole‐cell patch‐clamp ,Research Articles ,Neurons ,Sex Characteristics ,General Neuroscience ,G‐protein‐coupled receptor 30 ,Brain ,Receptors, Estrogen ,Child, Preschool ,Excitatory postsynaptic potential ,Female ,Research Article ,Agonist ,Adult ,medicine.medical_specialty ,18F‐FDG Positron emission tomography‐computerized tomography ,Adolescent ,medicine.drug_class ,Down-Regulation ,Pathology and Forensic Medicine ,03 medical and health sciences ,Young Adult ,Fluorodeoxyglucose F18 ,Seizures ,Internal medicine ,medicine ,Animals ,Humans ,Neuroinflammation ,business.industry ,standardized uptake values ,Cortical dysplasia ,medicine.disease ,focal cortical dysplasia type IIb ,Mice, Inbred C57BL ,030104 developmental biology ,Endocrinology ,Malformations of Cortical Development, Group I ,Neurology (clinical) ,Radiopharmaceuticals ,business ,030217 neurology & neurosurgery - Abstract
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 18F‐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.
- Published
- 2021