Abstracts

Rationale: Medical intractability, i.e. the absence of any response to anti-epileptic drug (AED) therapy, is an unresolved problem in many patients with epilepsy. Mechanisms of intractability are not well understood, but may include alterations of pharmacological targets and poor penetration of AEDs into the brain because of increased expression of multiple drug-resistance proteins, such as P-glycoprotein (Pgp; ABCB1). The aim of the present work was to evaluate the modifications in the RNAm expression of GABAA receptor subunits and their transporter in the tissue of patients with refractory temporal lobe epilepsy. Methods: For this study 14 cases of patients were included who suffered surgery by ELT and hippocampal sclerosis and 4 controls obtained by autopsy.Total RNA of hippocampus and cerebral cortex were obtained (fenol-chloroform method). The expression of the mRNA was analyzed by means of PCR-RT and quantified by densitometry with respect to B-actin (control gene). Results: The results showed modifications in the mRNA expression of GABAA receptor subunits, mRNA levels of the subunit alpha-1 were significantly enhanced, and reduction in mRNA-expression was observed of the GAT-3 transporter, alfa-2, 3 y 6, beta-1 y 2, and gamma-1 in the hippocampus, whereas mRNA-expression was increased in cerebral cortex of Gat-1, alpha-2, 4 and 6, beta-1 and 3, gamma-1 and 2, and reduction in mRNA-expression of gamma-3. Conclusions: The changes in the expression of the mRNA of the transporters (Gat-1 and Gat-3) and GABAA receptor subunits indicate that probably are generated adaptative changes in the epileptic brain that induced changes in sensitivity receptor or in the efficiency of receptor coupling the drugs. This project was supported by FIS/IMSS/PROT/548 grant