title: Altered expression of hypoxia-Inducible factor-1α participates in the epileptogenesis in animal models.
abstract: Although epilepsy is a common neurological disorder, its mechanism(s) are still not completely understood. Hypoxia can lead to neuronal cell death and angiogenesis, and the same mechanisms were also found in epilepsy. Hypoxia-inducible factor-1α (HIF-1α) is an important transcription protein that regulates gene expression in the brain and other tissues in response to decreases in oxygen availability. However, little is known regarding the expression of HIF-1α in the epileptic brain and whether HIF-1α interventions affect the epileptic process. The aims of this study are to investigate the expression profile of HIF-1α in rat models and to explore the role of HIF-1α in epilepsy. We performed Western blots and immunofluorescence in a lithium-pilocarpine rat epilepsy model. To determine the role of HIF-1α in epilepsy, we used the HIF-1α agonist DMOG and inhibitor KC7F2 to detect changes in the animal behavior in pentylenetetrazole (PTZ) and lithium-pilocarpine epilepsy models. The expression of HIF-1α was significantly increased after pilocarpine-induced status epilepticus. DMOG significantly prolonged the latent period in the PTZ kindling model and decreased the rate of spontaneous recurrent seizures during the chronic stage in the lithium-pilocarpine model. Conversely, the inhibitor KC7F2 produced an opposite behavioral change. Interestingly, both KC7F2 and DMOG had no effect on the acute stage of pilocarpine model and PTZ convulsive model. Our study suggests that upregulated HIF-1α may be involved in the process of epileptogenesis but not in the acute stage of epilepsy. The modulation of HIF-1α may offer a novel therapeutic target in epilepsy.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing, 400016, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Guohui
authors.initials: G
authors.lastname: Jiang
authors.forename: Yalan
authors.initials: Y
authors.lastname: Chen
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.forename: Zengyou
authors.initials: Z
authors.lastname: Li
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Wang
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Wang
mesh_terms: D000208:Acute Disease; D000600:Amino Acids, Dicarboxylic / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D002491:Central Nervous System Agents / Q000494:pharmacology; D002908:Chronic Disease; D004195:Disease Models, Animal; D004220:Disulfides / Q000494:pharmacology; D004827:Epilepsy / Q000188:drug therapy / Q000503:physiopathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018020:Lithium Compounds; D008297:Male; D010433:Pentylenetetrazole; D010862:Pilocarpine; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000188:drug therapy / Q000503:physiopathology; D013226:Status Epilepticus / Q000188:drug therapy / Q000503:physiopathology; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D000600:Amino Acids, Dicarboxylic; D002491:Central Nervous System Agents; D004220:Disulfides; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C545729:KC7F2 compound; D018020:Lithium Compounds; D013449:Sulfonamides; D010862:Pilocarpine; C040947:oxalylglycine; D010433:Pentylenetetrazole
keywords: epilepsy; hypoxia-inducible factor-1α; spontaneous recurrent seizures