Repulsive guidance molecule a suppresses seizures and mossy fiber sprouting via the FAK‑p120RasGAP‑Ras signaling pathway

Song,Mingyu; Tian,Fafa; Xia,Huang; Xie,Yuanyuan

doi:10.3892/mmr.2019.9951

Repulsive guidance molecule a suppresses seizures and mossy fiber sprouting via the FAK‑p120RasGAP‑Ras signaling pathway

Authors:
- Mingyu Song
- Fafa Tian
- Huang Xia
- Yuanyuan Xie
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Affiliations: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
Published online on: February 14, 2019 https://doi.org/10.3892/mmr.2019.9951
Pages: 3255-3262

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Abstract

Repulsive guidance molecule a (RGMa) is a membrane‑associated glycoprotein that regulates axonal guidance and inhibits axon outgrowth. In our previous study, we hypothesized that RGMa may be involved in temporal lobe epilepsy (TLE) via the repulsive guidance molecule a (RGMa)‑focal adhesion kinase (FAK)‑Ras signaling pathway. To investigate the role of RGMa in epilepsy, recombinant RGMa protein and FAK inhibitor 14 was intracerebroventricularly injected into a pentylenetetrazol (PTZ) kindling model and Timm staining, co‑immunoprecipitation and western blotting analyses were subsequently performed. The results of the present study revealed that intracerebroventricular injection of recombinant RGMa protein reduced the phosphorylation of FAK (Tyr397) and intracerebroventricular injection of FAK inhibitor 14 reduced the interaction between FAK and p120GAP, as wells as Ras expression. Recombinant RGMa protein and FAK inhibitor 14 exerted seizure‑suppressant effects; however, recombinant RGMa protein but not FAK inhibitor 14 suppressed mossy fiber sprouting in the PTZ kindling model. Collectively, these results demonstrated that RGMa may be considered as a potential therapeutic agent for epilepsy, and that RGMa may exert the aforementioned biological effects partly via the FAK‑p120GAP‑Ras signaling pathway.

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