Abstracts

Rationale: Serotonin (5-hydroxytryptamine, 5-HT) has been involved in many cerebral disorders including epilepsy. Previous studies with PET reported decreased temporal 5-HT1A binding ipsilateral to seizure foci in patients with temporal lobe epilepsy (TLE) (Toczek et al. Neurology 2003; 60:749-756). However, hitherto little is known about studies on the binding properties of the 5-HT1A receptor in epileptic hippocampus tissue of patients with pharmacoresistant TLE. In this study, we characterize the 5-HT1A receptor binding as well as G-protein activation mediated by these receptors in epileptic hippocampus of patients with pharmacoresistant. Methods: We obtained hippocampus tissue from 8 patients with TLE and brain tissue (hippocampus) of 5 autopsies from subjects who died from other causes different to neurological disease (Protocol approved by the scientific committee of the Hospital General of Mexico, DI/08/203/04/055). Competition binding experiments were performed using [3H]8-OH-DPAT (1 nM) to evaluate the binding and IC50 (concentration required to inhibit 50% to receptor). Binding assays of [35S]GTP S (0.05 nM) performed to evaluated the G-protein activation (Emax, expressed as % of stimulation of [35S]GTP S). Results: In contrast with autopsy samples (Emax= 74%), hippocampus obtained from patients with pharmacoresistant TLE demonstrated lower (Emax= 29%, p<0.05) 8-OH-DPAT-stimulated [35S]GTP S binding. Competition binding experiments revealed that both groups demonstrated similar binding (38.7 6.4 and 47.2 10.8 fmol/mg of protein, autopsy and TLE, respectively) and IC50 (1.2 0.21 and 0.83 0.12 nM, autopsy and TLE, respectively) values. Conclusions: Our present data provide strong evidence of alterations in G-protein activation mediated by these 5-HT1A receptors in epileptic hippocampus of patients with pharmacoresistant TLE. Alternatively, such changes may represent adaptive mechanisms to compensate for other as yet unknown alterations. Further studies are necessary to elucidate the role of intracellular changes associated with 5-HT1A receptor during the epilepsy process. This study was supported by the National Council for Sciences and Technology of Mexico (grants J110.0130/2009 and 98386).