The Correlation Study Between Dynamin1-mediated Endocytosis And Epilepsy

Objective: This study aims to investigate the expression pattern ofdynamin1in acute lithium–pilocarpine rat model and in patients withtemporal lobe epilepsy (TLE). Futhermore, specific inhibitor of dynamin1was used to explore the relationship between dynamin1and epilepticseizure in vivo and in vitro experiments.Methods: Our research group collected human brain tissues frompatients of temporal lobe epilepsy and the control human group, RT-PCRwas used to detect the mRNA levels of dynamin1gene, western blot andimmunofluorescence was used to examine dynamin1protein level andexpression sites. The above experiments were also used to investigatedynamin1expression change in the pilocarpine-induced rat model. Afterinjection of dynamin1specific inhibitor dynasore into the lateral ventricleand pilocarpine adminstration, behavioral changes were observed,patch-clamp technique was used to determine the effect of dynasore onepileptiform discharges.Results: Dynamin1mRNA and protein levels were up-regulated in pilocarpine-induced rat model at different time points (1d,3d,7d) whencompared with those in the control rat group. As compared to the humancontrol group, there appeared significant increased mRNA and protein levelof dynamin1in TLE patients. Dynamin1protein was mainly expressed incytoplasmic and axons of neurons but not in glial cells. Our study found thatsignificant increase of the seizure latency and decrease of seizure frequencywere observed in Dynasore10μM group. Dynasore at10μM significantlyreduced action potential frequency. As to the experiment of behavior studyand patch clamp, there were no significant difference between NS,DMSOand Dynaosre1, Dynasore160group.Conclusion: our study demonstrated that increased dynamin1expression was found both in acute seizure model of rats and patients withintractable TLE．Dynasore，the dynamin1specific inhibitors with certainconcentration (10μM) showed anticonvulsant effect on thepilocarpine-induced epileptic model and in vitro model. The resultsuggested that dynamin1may be related to epileptic seizue. In addition, itshowed anticonvulsant effects. However, further study should be neededto explore the specific anticonvulsant mechanism of dynasore.