Glutamate transporter expression and function in human glial progenitors

Glia ◽  
2004 ◽  
Vol 45 (2) ◽  
pp. 133-143 ◽  
Author(s):  
Nicholas J. Maragakis ◽  
Joerg Dietrich ◽  
Victor Wong ◽  
Haipeng Xue ◽  
Margot Mayer-Proschel ◽  
...  
2005 ◽  
Vol 280 (41) ◽  
pp. 34924-34932 ◽  
Author(s):  
Jürgen Zschocke ◽  
Nadhim Bayatti ◽  
Albrecht M. Clement ◽  
Heidrun Witan ◽  
Maciej Figiel ◽  
...  

2013 ◽  
Vol 2013 ◽  
pp. 1-16 ◽  
Author(s):  
Alexandra E. Schreiner ◽  
Eric Berlinger ◽  
Julia Langer ◽  
Karl W. Kafitz ◽  
Christine R. Rose

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 S100β 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 S100β 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.


2013 ◽  
Vol 62 (7) ◽  
pp. 973-981 ◽  
Author(s):  
Geraldine T. Petr ◽  
Ekaterina Bakradze ◽  
Natalie M. Frederick ◽  
Jianlin Wang ◽  
Wencke Armsen ◽  
...  

2017 ◽  
Vol 118 (1) ◽  
pp. 194-202 ◽  
Author(s):  
Joseph W. Salatino ◽  
Bailey M. Winter ◽  
Matthew H. Drazin ◽  
Erin K. Purcell

Microelectrode arrays implanted in the brain are increasingly used for the research and treatment of intractable neurological disease. However, local neuronal loss and glial encapsulation are known to interfere with effective integration and communication between implanted devices and brain tissue, where these observations are typically based on assessments of broad neuronal and astroglial markers. However, both neurons and astrocytes comprise heterogeneous cellular populations that can be further divided into subclasses based on unique functional and morphological characteristics. In this study, we investigated whether or not device insertion causes alterations in specific subtypes of these cells. We assessed the expression of both excitatory and inhibitory markers of neurotransmission (vesicular glutamate and GABA transporters, VGLUT1 and VGAT, respectively) surrounding single-shank Michigan-style microelectrode arrays implanted in the motor cortex of adult rats by use of quantitative immunohistochemistry. We found a pronounced shift from significantly elevated VGLUT1 within the initial days following implantation to relatively heightened VGAT by the end of the 4-wk observation period. Unexpectedly, we observed VGAT positivity in a subset of reactive astrocytes during the first week of implantation, indicating heterogeneity in early-responding encapsulating glial cells. We coupled our VGLUT1 data with the evaluation of a second marker of excitatory neurons (CamKiiα); the results closely paralleled each other and underscored a progression from initially heightened to subsequently weakened excitatory tone in the neural tissue proximal to the implanted electrode interface (within 40 μm). Our results provide new evidence for subtype-specific remodeling surrounding brain implants that inform observations of suboptimal integration and performance. NEW & NOTEWORTHY We report novel changes in the local expression of excitatory and inhibitory synaptic markers surrounding microelectrode arrays implanted in the motor cortex of rats, where a progressive shift toward increased inhibitory tone was observed over the 4-wk observation period. The result was driven by declining glutamate transporter expression (VGLUT1) in parallel with increasing GABA transporter expression (VGAT) over time, where a reactive VGAT+ astroglial subtype made an unexpected contribution to our findings.


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