Abstracts

Rationale: The microRNAs (miRNAs) are small size endogenous non-coding RNAs that regulate the expression of target mRNAs at post-transcriptional level. To date, more than 1000 human miRNAs have been identified. miRNAs have been demonstrated to be involved in many cell functions implicated in epilepsy and epileptogenesis, including cell death, neurogenesis, synaptic plasticity. Thus, understanding which specific miRNAs are differentially expressed in epilepsy may help to identify the mechanisms underlying the disease. Moreover, these miRNAs may represent biomarkers that identify specific subpopulations of epileptic patients, holding a prognostic value. Methods: In the present study, we examined the expression of more than 1,000 human miRNAs in the dentate gyrus granular layer. The granule cell layer of 10 patients who underwent surgery for intractable temporal lobe epilepsy was laser-microdissected from hippocampal paraffin-embedded sections. Total RNA was extracted from tissues and the miRNAome profile was obtained using an Agilent miRNA microarray. The study was performed in accordance with the recommendations of the international guidelines for human research and approved by the local Ethical Committee. Results: All patients had type 1a-1b mesial temporal sclerosis (Blümcke et al., Acta Neuropathol.,2007, 113:235-244), which was associated with no granule cell pathology (no GCP) in 5 patients and with granule cell dispersion (GCP type 2) in the other 5 (Blümcke et al., Acta Neuropathol., 2009, 117:535-544). The two groups of patients were similar for age, gender, clinical features of the disease. We identified 12 miRNAs that were differentially expressed in the two subgroups. Five of these are currently verified in an extended cohort of patients using RT-qPCR. Conclusions: This miRNA signature may be useful for a prognostic evaluation and forms the basis for further mechanistic studies that may lead to the identification of new therapeutic targets.