Regional Deafferentiation Down-Regulates Subtypes of Glutamate Transporter Proteins |
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Authors: | Stephen D. Ginsberg,&dagger Lee J. Martin, &Dagger Jeffrey D. Rothstein |
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Affiliation: | Departments of Pathology,; Neuroscience, and; Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A. |
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Abstract: | Abstract: Low extracellular glutamate content is maintained primarily by high-affinity sodium-dependent glutamate transport. Three glutamate transporter proteins have been cloned: GLT-1 and GLAST are astroglial, whereas EAAC1 is neuronal. The effects of axotomy on glutamate transporter expression was evaluated in adult rats following unilateral fimbria-fornix and corticostriatal lesions. The hippocampus and striatum were collected at 3, 7, 14, and 30 days postlesion. Homogenates were immunoblotted using antibodies directed against GLT-1, GLAST, EAAC1, and glial fibrillary acidic protein and assayed for glutamate transport by d -[3H]aspartate binding. GLT-1 immunoreactivity was decreased within the ipsilateral hippocampus and striatum at 14 days postlesion. GLAST immunoreactivity was decreased within the ipsilateral hippocampus and striatum at 7 and 14 days postlesion. No alterations in EAAC1 immunoreactivity were observed. d -[3H]Aspartate binding was decreased at 14 days postlesion within the ipsilateral hippocampus and at 7 and 14 days postlesion within the ipsilateral striatum. By 30 days postlesion, glutamate transporters and d -[3H]aspartate binding returned to control levels. This study demonstrates the down-regulation of primarily glial, and not neuronal, glutamate transporters following regional disconnection. |
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Keywords: | Glutamate transporter GLT-1 GLAST EAAC1 Fimbria-fornix Corticostriatal pathway |
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