Abstracts

Rationale: Several experimental and clinical studies have suggested that microRNAs (miRs) could be potential epilepsy biomarkers. Nowadays, research has been focused in inflammation-associated miRs. MiR-22 exerts an anti-tumor, anti-inflammatory and neuroprotective role mainly  through the regulation of the ATP-gated ionotropic receptor P2X7R. Inhibition of miR-22 is associated with higher hippocampal levels of P2X7R and inflammatory cytokines. The seizure-induced overexpression of these proteins has already been demonstrated in different experimental and clinical studies.Nevertheless, the role of miR-22 in epilepsy development is still controversial since studies in animal models of Mesial Temporal Lobe Epilepsy (MTLE) have reported both up and downregulation of this miR in hippocampus. Our aim was to characterize miR-22 expression in serum of MTLE patients, as miR expression is very stable in biological fluids. Methods: We tested if serum levels of miR-22 were correlated with P2X7R and IL-1ß mRNA levels in the brain of MTLE-HS patients comparing to healthy controls. Circulating miR-22 levels and IL-1ß and P2X7R brain expression were quantified by Real-Time PCR techniques. Results: MiR-22 serum levels were decreased (p=0.029) in MTLE-HS patients (n=40 vs. n=48 controls), particularly in those refractory to treatment (p=0.015). Conversely, P2X7R expression was higher in the hippocampus and anterior temporal lobe (p=0.012) of MTLE-HS patients (n=23 vs. n=10 cadaveric controls). Pro-inflammatory cytokine, IL-1ß was also over-expressed in MTLE-HS patients (p=0.0002). Conclusions: To the best of our knowledge this is the first study to quantify miR-22 expression in MTLE-HS patients. Our results are supported by recent experiments (Jimenez- Mateos et al 2015) showing that miR-22 lower levels are associated with propagation of epileptic seizures.The putative implication of miR-22 de-repression of P2X7R in epileptogenesis and seizure propagation linked to exacerbation of inflammatory responses and excitatory over inhibitory neurotransmission unbalance (Barros-Barbosa et al, 2016) requires further elucidation. Nevertheless, our hypothesis is that the miR-22/P2X7R/IL-1ß axis may be a novel target for therapeutic intervention  in drug-resistant MTLE-HS.   Funding: Partially, supported by a BICE Tecnifar Grant.