Dysregulation of miR‑24‑3p and miR‑186‑5p and GABAA receptor expression in focal cortical dysplasia

Abstract

Spontaneous synaptic activity mediated by GABA_A receptor is associated with epileptogenicity in focal cortical dysplasia (FCD). miRNAs are potentially involved in the regulation of GABA_A receptor subunit expression and activity. This study aimed to determine the expression of miRNAs in FCD and correlate their expression level with mRNA levels of GABA_A receptor subunits. Expression of GABA_A receptor subunits (α1 and α4) and miRNAs (miR‑155‑5p, miR‑186‑5p, and miR‑24‑3p) were evaluated using real‑time PCR in resected brain samples from FCD patients. miRNA levels were also determined in the serum of FCD patients. Spontaneous GABA_A receptor‑mediated synaptic activity was measured using patch clamp technique. Significant increase in α1 and α4 subunit expression and miR‑155‑5p levels, while decrease in miR‑24‑3p and miR‑186‑5p levels, was observed in the brain samples of FCD. In the serum of FCD patients, miR‑155‑5p levels were increased, whereas miR‑24‑3p and miR‑186‑5p levels remained unaltered. Increased α4 subunit expression in FCD might be due to reduced levels of miR‑24‑3p and miR‑186‑5p. In addition, reduced miR‑186‑5p levels might be responsible for increased expression of α1 subunit. We also observed an increase in the spontaneous GABA_A receptor‑mediated synaptic transmission in FCD. In conclusion, dysregulation of miRNAs and GABA_A receptor expression suggest that these miRNAs may contribute to altered GABA_A receptor‑mediated synaptic activity in FCD.