Enhanced synaptic vesicle traffic in hippocampus of phenytoin-resistant kindled rats.

AIM: Intractable epilepsy is characterized of seizure resistance to the anti-epileptic drugs. The underlying mechanisms are still elusive. Alterations of synaptic vesicle traffic may be one of the candidate mechanisms.

METHODS: Phenytoin-resistant and phenytoin-non resistant epileptic rats were selected in the amygdala kindled adult male Wistar rats. Synaptotagmin-I and clathrin were determined by cDNA microarry analysis and Western blotting in the hippocampus of phenytoin-resistant and phenytoin-nonresistant kindled rats, which were associated with the exocytosis and endocytosis of the synaptic vesicle traffic.

RESULTS: Microarry analysis showed both synaptotagmin-I and clathrin mRNA were up-regulated at least 3.06 fold accompanied with their correspondent proteins increased by 52.3 +/- 6.4 % and 76.7 +/- 12.4 % respectively in the hippocampus of phenytoin-resistant rats as compared with those in phenytoin-nonresistant rats. There were no significant differences in plasma phenytoin concentrations between the two groups.

CONCLUSIONS: The increased expressions of synaptotagmin-I and clathrin in the hippocampus of phenytoin-resistant kindled rats play a role in the development of intractable epilepsy.