miR-128 regulates epilepsy sensitivity in mice by suppressing SNAP-25 and SYT1 expression in the hippocampus

Epilepsy is accompanied by abnormal neurotransmission, and microRNAs, as versatile players in the modulation of gene expression, are important in epilepsy pathology. Here, we found that miR-128 expression was elevated in the acute seizure phase and decreased during the recurrent seizure phase after status epilepticus in mice. Both SNAP-25 and SYT1 are regulated by miR-128 in vitro and in vivo. Overexpressing miR-128 in cultured neurons decreased neurotransmitter released by suppressing SNAP-25 and SYT1 expression. Anti-miR-128 injection before kainic acid (KA) injection increased the sensitivity of mice to KA-induced seizures, while overexpressing miR-128 at the latent and recurrent phases had a neuroprotective effect in KA-induced seizures. Our study shows for the first time that miR-128, a key regulator of neurotransmission, plays an important role in epilepsy pathology and that miR-128 might be a potential candidate molecular target for epilepsy therapy. •MiR-128 is decreased in KA induced recurrent seizures.•MiR-128 suppresses neurotransmission by targeting SNAP-25 and SYT1.•Knocking down miR-128 increases the sensitivity to KA stimulation.•Overexpressing miR-128 diminishes the recurrent seizures at the recurrent phases.