Enhanced synaptic vesicle traffic in hippocampus of phenytoin-resistant kindled rats.
OBJECTIVE
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.
Department of Neurology, The First Affiliated Hospital, Chongqing Medical University, Chongqing Key Laboratories of Neurology, Yuzhong, Chongqing, People's Republic of China. zkebin2008@yahoo.com.cn
Kebin
K
Zeng
Xuefeng
X
Wang
Yurong
Y
Wang
Yong
Y
Yan
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001692:Biological Transport; D002966:Clathrin / Q000096:biosynthesis* / Q000235:genetics; D004351:Drug Resistance; D004705:Endocytosis; D005089:Exocytosis; D006624:Hippocampus / Q000378:metabolism*; D007696:Kindling, Neurologic; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010672:Phenytoin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013572:Synaptic Vesicles / Q000378:metabolism*; D050863:Synaptotagmin I / Q000096:biosynthesis / Q000235:genetics
D000927:Anticonvulsants; D002966:Clathrin; D050863:Synaptotagmin I; D010672:Phenytoin