Effect of glycine transporter 1 inhibitor on epileptic seizures and cognitive dysfunction in epilepsy mice

Abstract

Objective To study the effect of glycine transporter 1 inhibitor M22 on epileptic seizures and cognitive dysfunction in epilepsy mice. Methods A total of 110 C57BL/6 mice were randomly divided into Normal control group (CON group, n=10), Model group (Mod group n=20), M22-1 group (n=20), M22-2 group (n=20), M22-3 group (n=20), M22-4 group (n=20) according to weight.The chronic epileptic model was established by intraperitoneal injection of PTZ(30 mg/kg). The mice in CON group was injected with normal saline(10 mg/kg). The mice in Mod group were intraperitoneally injected with normal saline (10 ml/kg) and were injected with PT2 30 min later.The mice in M22-1 group, M22-2 group, M22-3 group, M22-4 group were intraperitoneally injected with M22 of corresponding dose(10 mg/kg, 20 mg/kg, 40 mg/kg, 80 mg/kg)respectively, lasting for 2 weeks.Epilepsy seizures of mice in each group were recorded.The learning and memory function of epilepsy mice were evaluated by Morris water maze test .Then the mice were sacrificed and the apoptosis related proteins Bcl-2, Bax, Cyt-c in the cerebral cortex of mice were measured by Western blot. Results (1)The mortality kindling rate, epileptic seizure grade and rate of tonic clonus in M22-2 and M22-3 group were significantly lower than those in Mod, M22-1 and M22-4 group(all P 0.05). Conclusion M22 (40 mg/kg) has significant anti-epileptic effect and can effectively improve the cognitive dysfunction of epileptic mice, which may be related to the inhibition of neuronal apoptosis in mice. Key words: Epilepsy; Glycine transporter 1 inhibitor; M22; Cognitive function; Pentylenetetrazole