title: Changes in glutamate transporter expression in mouse forebrain areas following focal ischemia.
abstract: Dysfunction of glutamate transporters has been proposed to promote neuronal death in modelled cerebral ischemia. However, these studies have produced conflicting results and the changes in glutamate transporter expression have not yet been examined in a mouse focal ischemic stroke model. This study used quantitative real-time reverse-transcription polymerase chain reaction to examine glutamate transporter mRNA expression in the hippocampus, cortex and striatum in a mouse model of focal ischemic stroke induced by middle cerebral artery occlusion (MCAO). Effects on mRNA expression of glial (GLT-1, GLAST) and neuronal (EAAC1) glutamate transporters in these brain areas were assessed by comparing MCAO brains with sham-operated control brains. Changes in transporter proteins were also assessed by immunohistochemistry using specific antibodies to GLT-1 and GLAST. Following focal ischemia, GLT-1 mRNA expression was decreased significantly in the ipsilateral hippocampus and cortex compared to the sham-operated brains (p<0.05). There were no significant differences in GLAST or EAAC1 mRNA expression between MCAO and sham-operated brains. Immunohistochemistry also confirmed a marked reduction in GLT-1 immunoreactivity in the cortex and hippocampus. Down regulation of GLT-1 in these brain areas may impair normal clearance of synaptically-released glutamate and contribute to neural damage following focal ischemic insult.
authors.affiliation: Division of Cardiovascular and Neuronal Remodelling, Leeds Institute for Genetics, Health and Therapeutics, University of Leeds, Leeds, LS2 9JT, UK.
authors.forename: Pirusha
authors.initials: P
authors.lastname: Ketheeswaranathan
authors.forename: Neil A
authors.initials: NA
authors.lastname: Turner
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Spary
authors.forename: Trevor F C
authors.initials: TF
authors.lastname: Batten
authors.forename: Barry W
authors.initials: BW
authors.lastname: McColl
authors.forename: Sikha
authors.initials: S
authors.lastname: Saha
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000235:genetics / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000473:pathology*; D004195:Disease Models, Animal; D027341:Excitatory Amino Acid Transporter 1 / Q000235:genetics / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000235:genetics / Q000378:metabolism; D050580:Excitatory Amino Acid Transporter 3 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009422:Nervous System Diseases / Q000209:etiology; D016548:Prosencephalon / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D027322:Amino Acid Transport System X-AG; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D050580:Excitatory Amino Acid Transporter 3; D012333:RNA, Messenger; C493399:Slc1a1 protein, mouse