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. Th...

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Bibliographic Details
Published in:Brain research 2011-10, Vol.1418, p.93-103
Main Authors: Ketheeswaranathan, Pirusha, Turner, Neil A, Spary, Emma J, Batten, Trevor F.C, McColl, Barry W, Saha, Sikha
Format: Article
Language:English
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
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Summary: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.
ISSN:0006-8993
1872-6240
DOI:10.1016/j.brainres.2011.08.029