Glioma-Derived TSP2 Promotes Excitatory Synapse Formation and Results in Hyperexcitability in the Peritumoral Cortex of Glioma
| Autor: | Hai-Feng Shu, Xin Chen, Yao-Hui Wang, Yang Li, Wei Li, Si-Xun Yu, Chen Tao, Tian-Lan Huang, Kuang Yongqin |
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| Rok vydání: | 2021 |
| Předmět: |
Synaptogenesis
Epileptogenesis Pathology and Forensic Medicine 03 medical and health sciences Cellular and Molecular Neuroscience Epilepsy 0302 clinical medicine Seizures Glioma Cell Line Tumor medicine Animals Humans 030304 developmental biology 0303 health sciences Thrombospondin Neocortex Chemistry Brain Neoplasms General Medicine medicine.disease Cortex (botany) Rats medicine.anatomical_structure Neurology Synapses Excitatory postsynaptic potential Neurology (clinical) Thrombospondins Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Journal of neuropathology and experimental neurology. 80(2) |
| ISSN: | 1554-6578 |
| Popis: | Seizures are common in patients with glioma, especially low-grade glioma (LGG). However, the epileptogenic mechanisms are poorly understood. Recent evidence has indicated that abnormal excitatory synaptogenesis plays an important role in epileptogenesis. The thrombospondin (TSP) family is a key regulator of synaptogenesis. Thus, this study aimed to elucidate the role of TSP2 in epileptogenesis in glioma-related epilepsy. The expression of TSP2 was increased in tumor tissue specimens from LGG patients, and this increase may have contributed to an increase in the density of spines and excitatory synapses in the peritumoral area. A glioma cell-implanted rat model was established by stereotactic implantation of wild-type TSP2-expressing, TSP2-overexpressing or TSP2-knockout C6 cells into the neocortex. Similarly, an increase in the density of excitatory synapses was also observed in the peritumoral area of the implanted tumor. In addition, epileptiform discharges occurred in the peritumoral cortex and were positively correlated with the TSP2 level in glioma tissues. Moreover, α2δ1/Rac1 signaling was enhanced in the peritumoral region, and treatment with the α2δ1 antagonist gabapentin inhibited epileptiform discharges in the peritumoral cortex. In conclusion, glioma-derived TSP2 promotes excitatory synapse formation, probably via the α2δ1/Rac1 signaling pathway, resulting in hyperexcitability in the peritumoral cortical networks, which may provide new insight into the epileptogenic mechanisms underlying glioma-related epilepsy. |
| Databáze: | OpenAIRE |
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