Abstracts

Rationale: The main goal of the present study was to characterize the mRNA expression, binding and G protein activation mediated by mu opioid receptors (MOR) in epileptic hippocampus of patients with pharmacoresistant temporal lobe epilepsy (TLE). Methods: Epileptic hippocampal tissue was obtained from patients with intractable mesial TLE history. Epileptic patients had en block anterior lobectomy, ipsilateral to the epileptic focus at least 48 h after the last seizure. During the surgical procedure, hippocampal biopsies were collected immediately upon resection and quickly frozen in pulverized dry ice. Hippocampus obtained at autopsy from subjects with no evidence of neurological disease was used as controls. The human hippocampus tissue was used to evaluate MOR and GAPDH mRNA expression, saturation binding and 35S-GTP?S functional assays. Results: In contrast with autopsy samples, hippocampus obtained from patients with epilepsy demonstrated enhanced MOR mRNA expression (116%). Saturation binding experiments revealed that the Bmax value from the epilepsy group was significantly higher (60%) when compared with autopsy samples, whereas the Kd values from both groups were not statistically different. DAMGO-stimulated 35S-GTP?S binding values from epilepsy group did not demonstrate significant alterations when they were compared with values obtained from autopsies of subjects with similar range of age. However, epileptic group demonstrated high levels of basal binding for the G proteins (136%). Conclusions: In conclusion, our present data provide strong evidence that the epileptic hippocampus of patients with TLE presents significant alterations in MOR mRNA, binding and signal transduction mechanisms downstream of these receptors. Alternatively, such changes may represent adaptive mechanisms to compensate for other as yet unknown alterations.