Department of Neurosurgery, Epilepsy Research Center of PLA, Xinqiao Hospital, Army Medical University, Chongqing, PR China.
Department of Pediatric Neurosurgery, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing Key Laboratory of Pediatrics, Chongqing, PR China.
Histol Histopathol. 2024 Sep;39(9):1179-1195. doi: 10.14670/HH-18-707. Epub 2024 Jan 10.
Tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) type IIb are the predominant causes of drug-refractory epilepsy in children. Dysmorphic neurons (DNs), giant cells (GCs), and balloon cells (BCs) are the most typical pathogenic profiles in cortical lesions of TSC and FCD IIb patients. However, mechanisms underlying the pathological processes of TSC and FCD IIb remain obscure. The Plexin-B2-Sema4C signalling pathway plays critical roles in neuronal morphogenesis and corticogenesis during the development of the central nervous system. However, the role of the Plexin-B2 system in the pathogenic process of TSC and FCD IIb has not been identified. In the present study, we investigated the expression and cell distribution characteristics of Plexin-B2 and Sema4C in TSC and FCD IIb lesions with molecular technologies. Our results showed that the mRNA and protein levels of Plexin-B2 expression were significantly increased both in TSC and FCD IIb lesions versus that in the control cortex. Notably, Plexin-B2 was also predominantly observed in GCs in TSC epileptic lesions and BCs in FCD IIb lesions. In contrast, the expression of Sema4C, the ligand of Plexin-B2, was significantly decreased in DNs, GCs, and BCs in TSC and FCD IIb epileptic lesions. Additionally, Plexin-B2 and Sema4C were expressed in astrocytes and microglia cells in TSC and FCD IIb lesions. Furthermore, the expression of Plexin-B2 was positively correlated with seizure frequency in TSC and FCD IIb patients. In conclusion, our results showed the Plexin-B2-Sema4C system was abnormally expressed in cortical lesions of TSC and FCD IIb patients, signifying that the Plexin-B2-Sema4C system may play a role in the pathogenic development of TSC and FCD IIb.
结节性硬化症复合征 (TSC) 和局灶性皮质发育不良 (FCD) IIb 是儿童药物难治性癫痫的主要原因。畸形神经元 (DNs)、巨细胞 (GCs) 和气球样细胞 (BCs) 是 TSC 和 FCD IIb 患者皮质病变中最典型的致病特征。然而，TSC 和 FCD IIb 病理过程的机制仍不清楚。Plexin-B2-Sema4C 信号通路在中枢神经系统发育过程中对神经元形态发生和皮质发生起着至关重要的作用。然而，Plexin-B2 系统在 TSC 和 FCD IIb 的致病过程中的作用尚未确定。在本研究中，我们使用分子技术研究了 Plexin-B2 和 Sema4C 在 TSC 和 FCD IIb 病变中的表达和细胞分布特征。我们的结果表明，与对照皮质相比， Plexin-B2 的 mRNA 和蛋白水平在 TSC 和 FCD IIb 病变中均显著增加。值得注意的是，Plexin-B2 也主要存在于 TSC 癫痫病变的 GCs 和 FCD IIb 病变的 BCs 中。相比之下， Plexin-B2 的配体 Sema4C 在 TSC 和 FCD IIb 癫痫病变中的 DNs、GCs 和 BCs 中的表达显著降低。此外，Plexin-B2 和 Sema4C 在 TSC 和 FCD IIb 病变中的星形胶质细胞和小胶质细胞中表达。此外，Plexin-B2 的表达与 TSC 和 FCD IIb 患者的癫痫发作频率呈正相关。总之，我们的结果表明， Plexin-B2-Sema4C 系统在 TSC 和 FCD IIb 患者的皮质病变中异常表达，表明 Plexin-B2-Sema4C 系统可能在 TSC 和 FCD IIb 的致病发展中起作用。
