Enhanced Synaptic Vesicle Traffic in Hippocampus of Phenytoin-Resistant Kindled Rats
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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.
KeywordsIntractable epilepsy Synaptotagmin-I Clathrin Vesicle traffic
This work was supported by the Chinese National Institutes of Health Grants 98013457 to Dr. Xuefeng Wang and Natural Science Fund of Chongqing 08046 to Dr. Kebin Zeng.
- 12.Guo X, Yang G (2004) Affection of freezing store on the determination of phenytoin and carbamazepinein human plasma. J Henan Univ 23:22–23 Medical ScienceGoogle Scholar
- 20.Li L, Chin LS, Shupliakov O, Brodin L, Sihra TS, Hvalby O, Jensen V, Zheng D, McNamara JO, Greengard P (1995) Impairment of synaptic vesicle clustering and of synaptic transmission, and increased seizure propensity, in synapsin I-deficient mice. Proc Natl Acad Sci USA 92:9235–9239. doi: 10.1073/pnas.92.20.9235 PubMedCrossRefGoogle Scholar