2-Deoxy-D-Glucose Exhibits Anti-seizure Effects by Mediating the Netrin-G1-KATP Signaling Pathway in Epilepsy

Epilepsy is a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures. The glycolytic inhibitor 2-deoxy-D-glucose (2-DG) has been reported to exert antiepileptic effects by upregulating KATP subunits (kir6.1 and kir6.2). We evaluated whether 2-DG exhibits anti-seizure effect by mediating the netrin-G1-KATP signaling pathway in epilepsy. In a mouse epilepsy model induced by lithium chloride-pilocarpine, 2-DG intervention increased the mRNA and protein expression levels of kir6.1 and kir6.2, and these increases were significantly reversed after knocking down netrin-G1 expression. Similarly, in cultured neurons with a magnesium-free medium, we found that the frequency of spontaneous postsynaptic potentials (SP) was increased, and in the meanwhile, expression levels of kir6.1 and kir6.2 were increased after pretreatment with 2DG. These effects were remarkably reversed after knocking down netrin-G1. Thus, our findings show that 2DG exhibits anti-seizure effects through the netrin-G1-KATP signaling pathway.