Lesion-Induced Alterations in Astrocyte Glutamate Transporter Expression and Function in the Hippocampus. (3rd September 2013)

• Record Type: Journal Article
• Authors: Schreiner, Alexandra E.; Berlinger, Eric; Langer, Julia; Kafitz, Karl W.; Rose, Christine R.
• Other Names: Barnett S. C. Academic Editor.; Satoh J.-i. Academic Editor.
• Is Part Of: ISRN neurology. Volume 2013(2013)
• Publication Date: 2013-09-03
• Subjects: Neurology -- Periodicals; Nervous System Diseases; Neurology; Neurology; Periodicals; 616.8
• DOI: 10.1155/2013/893605
• Languages: English
• ISSNs: 2090-5505

Abstract

Abstract : Astrocytes express the sodium-dependent glutamate transporters GLAST and GLT-1, which are critical to maintain low extracellular glutamate concentrations. Here, we analyzed changes in their expression and function following a mechanical lesion in the CA1 area of organotypic hippocampal slices. 6-7 days after lesion, a glial scar had formed along the injury site, containing strongly activated astrocytes with increased GFAP and S100 β immunoreactivity, enlarged somata, and reduced capability for uptake of SR101. Astrocytes in the scar's periphery were swollen as well, but showed only moderate upregulation of GFAP and S100 β and efficiently took up SR101. In the scar, clusters of GLT-1 and GLAST immunoreactivity colocalized with GFAP-positive fibers. Apart from these, GLT-1 immunoreactivity declined with increasing distance from the scar, whereas GLAST expression appeared largely uniform. Sodium imaging in reactive astrocytes indicated that glutamate uptake was strongly reduced in the scar but maintained in the periphery. Our results thus show that moderately reactive astrocytes in the lesion periphery maintain overall glutamate transporter expression and function. Strongly reactive astrocytes in the scar, however, display clusters of GLAST and GLT-1 immunoreactivity together with reduced glutamate transport activity. This reduction might contribute to increased extracellular glutamate concentrations and promote excitotoxic cell damage at the lesion site.