Differential expression of miR-34a, 451, 1260, 1275 and 1298 in the neocortex of patients with mesial temporal lobe epilepsy

Abstract

Mesial temporal lobe epilepsy (mTLE) is the most common epilepsy syndrome which will eventually become pharmacologically intractable partial-onset seizures. Regulation of gene expression is an important process in the development of this pathology where microRNAs (miRs) are involved. The role of miRs has been widely studied in the hippocampus of rodents and patients. However, little is known about its differential expression in other brain regions such as the neocortex. The temporal neocortex plays a major role in the generation and propagation of seizures and in synaptic disruption, impairing the excitatory and inhibitory balance. Therefore, we assessed the expression of miR-146a, 34a, 1260, 1275, 1298, 451, 132 and 142-3p in the neocortex of 12 patients with mTLE and compared them with miRs expression found in 10 control samples. We noted a significant decrease in the expression of miR-34a and 1298 in patients with mTLE and a -1.49 to -7.0 fold change respectively compared with controls. Conversely, we observed a significant increase in the expression of miR-451, 1260 and 1275 in patients with a 25.67, 4.09 and a 7.07 fold change respectively compared to controls. Using Pearson correlation, we explored the association between the clinical features of mTLE patients and controls with miRs expression. In the control group we found a significant correlation only with age and miR-146a expression (r = 0.733). The analysis of mTLE patients showed a negative correlation between expression of miR-1260 (r = -0.666) and miR-1298 (r = -0.651) and age. Furthermore, we found a positive correlation between miR-146a expression with seizure frequency (r = 0.803) and a positive correlation between miR-146a and 451 expression with number of antiepileptic drugs used for presurgical treatment (r = 0.715 and 0.611 respectively), thus suggesting a positive correlation with disease severity. These miRs are associated with biological processes such as apoptosis, drug resistance, inflammation, inhibitory and excitatory synaptic transmission, axonal guidance and signaling of neurotrophins. Therefore, deepening our understanding of the targets involved in these miRs will help to elucidate the role of the neocortex in epilepsy.

Keywords: Epilepsy; Pharmacoresistance; Temporal neocortex; mTLE; miR.