Abnormal Expression Of SrGAP2 In The Brain Of Patients With Intractable Epilepsy And Pilocarpine-induced Seizures In Rats

Objective:srGAP2 is an important RhoGAP molecule of the Slit-Robo downstream signal pathway, and plays a role in synapse formation and maintenance. Our study researched the possible correlation between srGAP2 expression and epilepsy pathogenesis on the numerator level, through tested the expression of srGAP2 in temporal lobe epileptic foci from patients with intractable epilepsy and experimental rats.Methods:We selected thirty-five surgical samples of temporal neocortex from patients with intractable epilepsy and fifteen autopsy samples of normal human brain from individuals who died accidents. Fifty-six Sprague-Dawley male rats were divided randomly into seven groups, including six groups with epilepsy induced by lithium-pilocarpine management and one control group. The samples of temporal lobe tissue were taken from rats at 6h, Id, 1w,2w, 1m, and 2m time-points, and from controls group. Using immunohistochemistry, immunefluorescence, and western-blot methods, we tested the expression of srGAP2 in intractable epilepsy patients, experimental animals, and their respective control groups.Result:srGAP2 was expressed in the membrane and cytoplasm of neurons from control group, and expression was significantly higher in temporal lobe tissue from patients with intractable epilepsy as compared with the controls. Western blotting of rat brain tissue showed that srGAP2 was up-regulated beginning at 6h after kindling. The maximal expression was seen around 2w, and relatively high expression was maintaining until 1m. The expression then returned down, and approached normal levels at 2m.These results were consistent with the immunohistochemical and immunofluorescence results.Conclusions:These data implicate srGAP2 may promote MFS, and participate in the abnormal development of synapses. The result suggests that this protein may play an important role in the pathogenesis of intractable epilepsy.