Gene expression profile suggests different mechanisms underlying sporadic and familial mesial temporal lobe epilepsy

Abstract

Most patients with pharmacoresistant mesial temporal lobe epilepsy (MTLE) have hippocampal sclerosis on the postoperative histopathological examination. Although most patients with MTLE do not refer to a family history of the disease, familial forms of MTLE have been reported. We studied surgical specimens from patients with MTLE who had epilepsy surgery for medically intractable seizures. We assessed and compared gene expression profiles of the tissue lesion found in patients with familial MTLE ( n = 3) and sporadic MTLE ( n = 5). In addition, we used data from control hippocampi obtained from a public database ( n = 7). We obtained expression profiles using the Human Genome U133 Plus 2.0 (Affymetrix) microarray platform. Overall, the molecular profile identified in familial MTLE differed from that in sporadic MTLE. In the tissue of patients with familial MTLE, we found an over-representation of the biological pathways related to protein response, mRNA processing, and synaptic plasticity and function. In sporadic MTLE, the gene expression profile suggests that the inflammatory response is highly activated. In addition, we found enrichment of gene sets involved in inflammatory cytokines and mediators and chemokine receptor pathways in both groups. However, in sporadic MTLE, we also found enrichment of epidermal growth factor signaling, prostaglandin synthesis and regulation, and microglia pathogen phagocytosis pathways. Furthermore, based on the gene expression signatures, we identified different potential compounds to treat patients with familial and sporadic MTLE. To our knowledge, this is the first study assessing the mRNA profile in surgical tissue obtained from patients with familial MTLE and comparing it with sporadic MTLE. Our results clearly show that, despite phenotypic similarities, both forms of MTLE present distinct molecular signatures, thus suggesting different underlying molecular mechanisms that may require distinct therapeutic approaches.

Introduction to the thematic issue: Recognition of women leaders in Science

“…2 They now provide evidence that, despite their phenotypic similarities, the familial and sporadic forms of this disease may possess differing underlying molecular mechanisms. 3 Based on the mRNA expression signatures in the tissue lesions of carefully diagnosed and characterized patients, the authors describe an elevated expression of biological pathways related to protein response, mRNA processing and synaptic plasticity in familial MTLE. The gene expression profile of the hippocampi from sporadic MTLE patients suggests a highly activated inflammatory response in these individuals.…”