Abstracts

Rationale: Recently, we identified the first locus for familial mesial temporal lobe epilepsy (MTLE) associated with hippocampal atrophy (HA), which strongly suggests that HA may also have a genetic predisposition. Surgical specimens of patients with intractable MTLE, offer a unique opportunity to address questions related to the pathophysiology of HA in the context of MTLE. The aim of this study was to perform gene expression studies in tissue samples from familial MTLE patients who underwent surgery for medically intractable seizures.Methods: This study was performed using Human Genome U133 Plus 2.0 array (Affymetrix™). High-quality total RNA from one control hippocampus (from autopsy) and three surgical specimens (from pharmacoresistant epilepsy patients) were isolated by TRIzol (Invitrogen–Life Technologies™). We used 6 µg of starting material in the one-cycle target labeling protocol (Affymetrix™). Data was acquired by GeneChip Scanner 3000 (Affymetrix™) and analyzed using MAS5.0 expression measure (Affymetrix ™).Results: Comparison between control and disease hippocampi identified 2300 genes which were differently expressed and they are related to many cell functional classes, such as transcription factors, enzymes, signaling and structural function. Interesting, among these we identified five genes which were present in disease hippocampi, not present in control specimen and are localized within the candidate region for familial MTLE identified on chromosome 18p: ADCYAP1, TYMS, DLGAP1, PTPRM and YES1. Conclusions: Our study brings functional information related to gene expression profile into the current efforts to unravel the molecular mechanism responsible for familial MTLE associated with HA. Additional studies are underway in order to compare gene expression profile of familial and non-familial MTLE hippocampi. Support: FAPESP and CNPq