Effect of alpha-asarone on regulation of GABA system in the Lithium-Pilocarpine model of epilepsy

Aim To investigate the molecular mechanism of antiepileptic effect of alpha-asarone on Lithium-Pilocarpine model.Methods Rat status epilepticus(SE) model was induced by Lithium-Pilocarpine.Rats were sacrificed at the 12 h,24 h,48 h,72 h and 1 week after SE to dynamically observe GABA content,GAD67 expression,GABA transaminase(GABA-T) activity and expression of GABAA receptor.The effect of alpha-asarone on these changes was observed.Results GABA content and GAD67 expression in the hippocampus were markedly decreased at 12 h~24 h(P0.01) and increased gradually after 72 h.The GABA-T activities in the frontal lobes,especially the hippocampus,were significantly increased at different time point(P0.05) and still higher than those in normal control group at one week post-SE.At12 h~24 h after SE,the expression of GABAAR-mRNA were significantly lower in Lithium-Pilocarpine model group than in normal control group(P0.01).The expression of GABAAR-mRNA were markedly increased and reached to maximum level at 48 h～72 h post-SE.The content of GABA and the expression of GAD67 and GABAAR-mRNA were significantly higher in alpha-asarone treated group than in Lithium-Pilocarpine model group at 12h～7d post-SE(P0.05).The activity of GABA-T in the frontal lobes and the hippocampus were significantly lower in alpha-asarone treated group than in Lithium-Pilocarpine model group at different time point(P0.05).Conclusions The antiepileptic effect of alpha-asarone seems to be directly related to its role in upregulating GABA content and the expression of GAD67 and GABAAR mRNA,and down regulating GABA-T activity.