title: The antiepileptic effect of the glycolytic inhibitor 2-deoxy-D-glucose is mediated by upregulation of K(ATP) channel subunits Kir6.1 and Kir6.2.
abstract: Metabolic modulation of neuronal excitability is becoming increasingly important as an antiepileptic therapy. It was reported that the glycolytic inhibitor 2-deoxy-D-glucose (2-DG) and the activation of the ATP-sensitive potassium ion channel (K(ATP) channel) had an antiepileptic effect in models of epilepsy. To explore whether 2-DG exerts an antiepileptic effect through upregulation of the K(ATP) channel subunits Kir6.1 and Kir6.2, the expression of these subunits in hippocampus of five groups of mice with pilocarpine-induced status epilepticus (SE) was evaluated. A seizure group with pilocarpine-kindling convulsions (EP) was compared to similar groups treated with high, medium, and low 2-DG concentrations (100-500 mg/kg) and a normal control group (Con). Kir6.1 and Kir6.2 mRNAs and proteins were analyzed at 4 h, 1 days (acute period), 7 days (latent period), 30, and 60 days (chronic period) following SE. In the seizure group (compared to the Con group), hippocampal expression of Kir6.1 and Kir6.2 increased dramatically at 1, 7, and 30 days, and was further increased after treatment with medium and high dose 2-DG (all P < 0.05). Our results suggest that 2-DG may exert an antiepileptic effect through up-regulation of mRNAs and protein levels of Kir6.1 and Kir6.2, which may therefore be used as molecular targets in the treatment of epilepsy with 2-DG.
authors.affiliation: Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, 410013 Hunan, People's Republic of China.
authors.forename: Heng
authors.initials: H
authors.lastname: Yang
authors.forename: Ren
authors.initials: R
authors.lastname: Guo
authors.forename: Jiongxing
authors.initials: J
authors.lastname: Wu
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Peng
authors.forename: Dujie
authors.initials: D
authors.lastname: Xie
authors.forename: Wen
authors.initials: W
authors.lastname: Zheng
authors.forename: Xian
authors.initials: X
authors.lastname: Huang
authors.forename: Ding
authors.initials: D
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Lihua
authors.initials: L
authors.lastname: Huang
authors.forename: Zhi
authors.initials: Z
authors.lastname: Song
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000378:metabolism*; D003847:Deoxyglucose / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D006624:Hippocampus / Q000378:metabolism*; D054086:KATP Channels / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010862:Pilocarpine; D024661:Potassium Channels, Inwardly Rectifying / Q000096:biosynthesis*; D013226:Status Epilepticus / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D015854:Up-Regulation; D000099161:Kcnj11 Channel
chemical_list: D000927:Anticonvulsants; D003847:Deoxyglucose; D054086:KATP Channels; D010862:Pilocarpine; D024661:Potassium Channels, Inwardly Rectifying; D000099161:Kcnj11 Channel; C092520:uK-ATP-1 potassium channel