AI Article Synopsis
- Intractable epilepsy involves seizures that don't respond to typical anti-epileptic medications, and changes in synaptic vesicle trafficking may be a possible cause.
- Researchers studied the differences in synaptic proteins, specifically synaptotagmin-I and clathrin, in phenytoin-resistant versus non-resistant rats, finding significant increases in their levels in the resistant group.
- The findings suggest that elevated synaptotagmin-I and clathrin in the hippocampus might contribute to the development of this drug-resistant form of epilepsy.
Article Abstract
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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s11064-008-9856-9 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Gene Expression Analysis Identifies Cholesterol Metabolism Dysregulation in Hippocampus of Phenytoin-Resistant Pentylenetetrazol-Kindled Epileptic Mice.
Neuromolecular Med
December 2021
Epigenetics & Neuropsychiatric Disorders Laboratory, CSIR-Centre for Cellular and Molecular Biology (CCMB), Uppal Road, Habsiguda, Hyderabad, Telangana State, 500007, India.
Pharmaco-resistant Epilepsy has been a major challenge for medical interventions in controlling seizures. To date, up to 33% of the patients with epilepsy do not show adequate response to anti-epileptic drugs even after prolonged combinatorial drug usage. Using microarray, this study explores the changes in hippocampal gene expression in the phenytoin-resistant pentylenetetrazol (PTZ)-kindled mouse model of epilepsy.
View Article and Find Full Text PDFSubicular pyramidal neurons gate drug resistance in temporal lobe epilepsy.
Ann Neurol
October 2019
Institute of Pharmacology and Toxicology, Key Laboratory of Medical Neurobiology of National Health Commission and Chinese Academy of Medical Sciences, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
Objective: Drug-resistant epilepsy causes great clinical danger and still lacks effective treatments.
Methods: Here, we used multifaceted approaches combining electrophysiology, optogenetics, and chemogenetics in a classic phenytoin-resistant epilepsy model to reveal the key target of subicular pyramidal neurons in phenytoin resistance.
Results: In vivo neural recording showed that the firing rate of pyramidal neurons in the subiculum, but not other hippocampal subregions, could not be inhibited by phenytoin in phenytoin-resistant rats.
Effects of high frequency electrical stimulation and R-verapamil on seizure susceptibility and glutamate and GABA release in a model of phenytoin-resistant seizures.
Neuropharmacology
September 2011
Department of Pharmacobiology, Center for Research and Advanced Studies, Mexico City, Mexico.
The present study was focused to characterize the effects of intrahippocampal application of R-verapamil, a P-glycoprotein blocker, and High Frequency Electrical Stimulation (HFS) at 130 Hz, on seizure susceptibility and extracellular concentrations of glutamate and γ-aminobutyric acid (GABA) in hippocampus of kindled rats with drug-resistant seizures. Fully kindled rats classified in responsive and non-responsive to phenytoin were used for this purpose. In contrast with responsive animals, non-responsive rats showed lower afterdischarge threshold (ADT) values in pre-kindling conditions and required less number of kindling trials to achieve the kindled state.
View Article and Find Full Text PDFEnhanced synaptic vesicle traffic in hippocampus of phenytoin-resistant kindled rats.
Neurochem Res
May 2009
Department of Neurology, The First Affiliated Hospital, Chongqing Medical University, Chongqing Key Laboratories of Neurology, Yuzhong, Chongqing, People's Republic of China.
Article Synopsis
- Intractable epilepsy involves seizures that don't respond to typical anti-epileptic medications, and changes in synaptic vesicle trafficking may be a possible cause.
- Researchers studied the differences in synaptic proteins, specifically synaptotagmin-I and clathrin, in phenytoin-resistant versus non-resistant rats, finding significant increases in their levels in the resistant group.
- The findings suggest that elevated synaptotagmin-I and clathrin in the hippocampus might contribute to the development of this drug-resistant form of epilepsy.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!