title: Intermittent hypoxia preconditioning-induced epileptic tolerance by upregulation of monocarboxylate transporter 4 expression in rat hippocampal astrocytes.
abstract: Noxious stimuli applied at doses close to but below the threshold of cell injury induce adaptive responses that provide a defense against additional stress. Epileptic preconditioning protects neurons against status epilepticus and ischemia; however, it is not known if the converse is true. During hypoxia/ischemia (H/I), lactate released from astrocytes is taken up by neurons and is stored for energy, a process mediated by monocarboxylate transporter 4 (MCT4) in astroglia. The present study investigated whether H/I preconditioning can provide protection to neurons against epilepsy through upregulation of MCT4 expression in astrocytes in vitro and in vivo. An oxygen/glucose deprivation protocol was used in primary astrocyte cultures, while rats were subjected to an intermittent hypoxia preconditioning (IHP) paradigm followed by lithium-pilocarpine-induced epilepsy as well as lactate transportation inhibitor injection, with a subsequent evaluation of protein expression as well as behavior. H/I induced an upregulation of MCT4 expression, while an IHP time course of 5 days provided the greatest protection against epileptic seizures, which was most apparent by 3 days after IHP. However, lactate transport function disturbances can block the protective effect induced by IHP. These findings provide a potential basis for the clinical treatment of epilepsy.
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, Shanxi Province, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Gao
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.forename: Bei
authors.initials: B
authors.lastname: Liu
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.forename: Qianli
authors.initials: Q
authors.lastname: Yang
authors.forename: Jungong
authors.initials: J
authors.lastname: Jin
authors.forename: Huanfa
authors.initials: H
authors.lastname: Li
authors.forename: Shan
authors.initials: S
authors.lastname: Dong
authors.forename: Guodong
authors.initials: G
authors.lastname: Gao
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism*; D002478:Cells, Cultured; D004827:Epilepsy / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D000860:Hypoxia; D019194:Ischemic Preconditioning / Q000379:methods; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
chemical_list: D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; C516342:Slc16a3 protein, rat