Histol Histopathol, Vol 39, Dai et al.

Altered expression of the Plexin-B2 system in tuberous sclerosis complex and focal cortical dysplasia IIb lesions

Lu Dai¹*, Jun Huang¹*, Kai-feng Shen¹, Xiao-lin Yang¹, Gang Zhu¹, Li Zhang², Zhong-ke Wang³, Shi-yong Liu¹, Xiang Liao⁴, Sen-lin Xu⁵, Hui Yang^1,6, Xing-yi Li⁴ and Chun-qing Zhang¹

¹Department of Neurosurgery, Epilepsy Research Center of PLA, Xinqiao Hospital, Army Medical University, ²Department 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, ³Department of Neurosurgery, Armed Police Hospital of Chongqing, ⁴Center for Neurointelligence, School of Medicine, Chongqing University, ⁵Institute of Pathology, Southwest Hospital and ⁶Chongqing Institute for Brain and Intelligence, Guangyang Bay Laboratory, Chongqing, PR China
*Contributed equally

Corresponding Author: Chun-qing Zhang, Department of Neurosurgery, Epilepsy Research Center of PLA, Xinqiao Hospital, Army Medical University, 183 Xinqiao Main Street, Shapingba District, Chongqing 400037, PR China. e-mail: cqzhang@tmmu.edu.cn or Xing-yi Li, Center for Neurointelligence, School of Medicine, Chongqing University, No. 131 Yubei Road, Shapingba District, Chongqing 400030, China. e-mail: xingyi_li@cqu.edu.cn

Summary. 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. Histol Histopathol

Key words: Epilepsy, Malformation of cortical development, Plexin-B2, Sema4C

DOI: 10.14670/HH-18-707