Changes in glutamate transporter expression in mouse forebrain areas following focal ischemia

• Published in: Brain research Vol. 1418; pp. 93 - 103
• Main Authors: Ketheeswaranathan, Pirusha, Turner, Neil A, Spary, Emma J, Batten, Trevor F.C, McColl, Barry W, Saha, Sikha
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 18.10.2011; Elsevier
• Subjects: Amino Acid Transport System X-AG - genetics; Amino Acid Transport System X-AG - metabolism; Analysis of Variance; animal models; Animals; antibodies; Biological and medical sciences; Brain Ischemia - complications; Brain Ischemia - pathology; cortex; death; Disease Models, Animal; Excitatory Amino Acid Transporter 1 - genetics; Excitatory Amino Acid Transporter 1 - metabolism; Excitatory Amino Acid Transporter 2 - genetics; Excitatory Amino Acid Transporter 2 - metabolism; Excitatory Amino Acid Transporter 3 - genetics; Excitatory Amino Acid Transporter 3 - metabolism; gene expression; Gene Expression Regulation - genetics; Gene Expression Regulation - physiology; GLT-1; Glutamate transporter; glutamic acid; hippocampus; immunohistochemistry; ischemia; Male; Medical sciences; Mice; Mice, Inbred C57BL; Middle cerebral artery occlusion; Mouse; Nervous System Diseases - etiology; Neurology; Prosencephalon - metabolism; Prosencephalon - pathology; Quantitative real time PCR; reverse transcriptase polymerase chain reaction; RNA, Messenger - metabolism; Stroke; transporters; Vascular diseases and vascular malformations of the nervous system; MCAO; Stroke; AMPA; N-methyl- d-aspartate; qRT-PCR; PKC; excitatory amino acid carrier-1; glutamate-aspartate transporter; EAAT; GLAST; quantitative real-time reverse-transcription polymerase chain reaction; EAAC-1; excitatory amino acid transporter; Mouse; glutamate transporter-1; Glutamate transporter; NMDA; α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid; middle cerebral artery occlusion; protein kinase C; GLT-1; Quantitative real time PCR; Middle cerebral artery occlusion; Central nervous system; Cardiovascular disease; Vascular disease; Cerebrovascular disease; Carrier protein; Nervous system diseases; Rodentia; Gene expression; Glutamate; Cerebral disorder; Prosencephalon; Polymerase chain reaction; Vertebrata; Mammalia; Animal; Central nervous system disease; Excitatory aminoacid; Neurotransmitter; Brain ischemia
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2011.08.029

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.