Role of mTOR signaling pathway in glioma-associated seizures

Abstract

Objective To investigate the role of mTOR signaling pathway in glioma-associated seizures (GAS). Methods We retrospectively analyzed 12 glioma patients admitted to Department of Neurosurgery, West China Hospital, Sichuan University from January 2016 to June 2016. Among the 12 glioma patients, 9 had glioma GAS and 3 did not. All patients enrolled into this study underwent tumor resection. After surgery, the neuroelectrical activities of tumor tissue, peritumoral tissue and peritumoral normal tissue were documented by patch clamping recording of brain slices to clarify the GAS lesions, followed by Western blotting and immunohistochemical experiments to confirm whether mTOR pathway activation was related to GAS. Results Interictal-like discharges (ILDs) were observed in 7 of 12 peritumoral tissues obtained from patients with glioma who had experienced perioperative seizures. Their peak amplitude ranged from 0.300 mV to -0.429 mV and the slope was 1.502 mV/ms. However, their tumor and normal tissue samples didn′t show ILDs. No ILDs were observed in the tumor tissue, peritumoral or normal tissue of 2 patients with GAS and 3 patients without GAS. The results of Western blotting showed that peritumoral expressions of p-mTOR (relative expression value: 1.002) and p-S6K (relative expression value: 0.926) of patients with GAS were significantly higher than those of patients without GAS (relative expression Value: 0.756 and 0.661, both P 0.05). There was no statistical significance in the expression of p-mTOR, mTOR, p-S6K or S6K in the tumor tissues between patients with GAS and those without GAS (all P>0.05). Immunohistochemical staining results showed that p-S6K and p-mTOR stainings were positive in the peritumoral tissues in 8 of 9 patients with GAS, while they were negative in 3 patients without GAS. Both p-S6K and p-mTOR staining were positive in tumor tissues of patients with GAS and patients without GAS. Conclusions The mTOR pathway expression in peritumoral issues is associated with GAS, which thus provides a potential target for therapeutics aimed at simultaneously controlling gliomas and seizures. Key words: Glioma; Epilepsy; mTOR pathway