title: Regulation of astrocyte glutamate transporter-1 (GLT1) and aquaporin-4 (AQP4) expression in a model of epilepsy.
abstract: Astrocytes regulate extracellular glutamate and water homeostasis through the astrocyte-specific membrane proteins glutamate transporter-1 (GLT1) and aquaporin-4 (AQP4), respectively. The role of astrocytes and the regulation of GLT1 and AQP4 in epilepsy are not fully understood. In this study, we investigated the expression of GLT1 and AQP4 in the intrahippocampal kainic acid (IHKA) model of temporal lobe epilepsy (TLE). We used real-time polymerase chain reaction (RT-PCR), Western blot, and immunohistochemical analysis at 1, 4, 7, and 30days after kainic acid-induced status epilepticus (SE) to determine hippocampal glial fibrillary acidic protein (GFAP, a marker for reactive astrocytes), GLT1, and AQP4 expression changes during the development of epilepsy (epileptogenesis). Following IHKA, all mice had SE and progressive increases in GFAP immunoreactivity and GFAP protein expression out to 30days post-SE. A significant initial increase in dorsal hippocampal GLT1 immunoreactivity and protein levels were observed 1day post SE and followed by a marked downregulation at 4 and 7days post SE with a return to near control levels by 30days post SE. AQP4 dorsal hippocampal protein expression was significantly downregulated at 1day post SE and was followed by a gradual return to baseline levels with a significant increase in ipsilateral protein levels by 30days post SE. Transient increases in GFAP and AQP4 mRNA were also observed. Our findings suggest that specific molecular changes in astrocyte glutamate transporters and water channels occur during epileptogenesis in this model, and suggest the novel therapeutic strategy of restoring glutamate and water homeostasis.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of California, Riverside, USA.
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Hubbard
authors.affiliation: Neuroscience Graduate Program, University of California, Riverside, USA.
authors.forename: Jenny I
authors.initials: JI
authors.lastname: Szu
authors.affiliation: Neuroscience Graduate Program, University of California, Riverside, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Yonan
authors.affiliation: Neuroscience Graduate Program, University of California, Riverside, USA; Center for Glial-Neuronal Interactions, University of California, Riverside, USA; Division of Biomedical Sciences, School of Medicine, University of California, Riverside. Electronic address: dbinder@ucr.edu.
authors.forename: Devin K
authors.initials: DK
authors.lastname: Binder
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics / Q000378:metabolism*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D004569:Electroencephalography; D004827:Epilepsy / Q000139:chemically induced / Q000473:pathology*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D027342:Excitatory Amino Acid Transporter 2 / Q000235:genetics / Q000378:metabolism*; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology*; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
chemical_list: D051401:Aquaporin 4; D018690:Excitatory Amino Acid Agonists; D027342:Excitatory Amino Acid Transporter 2; D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; C493396:Slc1a2 protein, mouse; D007608:Kainic Acid
keywords: AQP4; Aquaporin; Astrocyte; EAAT2; Epilepsy; GFAP; GLT1; Glutamate transporter-1; Kainic acid; Seizure