Glutamate uptake is affected in the central nervous system of system xc- deficient mice

Thomas Demuyser, Stéphanie Goursaud, Eduard-Mihai Bentea, Joeri Van Liefferinge, Ellen Merckx, Ilse Julia Smolders, Ann Massie, Emmanuel Hermans

Onderzoeksoutput: Meeting abstract (Book)

Samenvatting

Glutamate uptake is affected in the central nervous system of system xc--deficient mice
T. Demuyser1, S. Goursaud2, E. Bentea1, J. Van Liefferinge1, E. Merckx1, I. Smolders1, A. Massie1 and E. Hermans2
1Vrije Universiteit Brussel, Brussels, 1090, Belgium and 2Université Catholique de Louvain, Woluwe Saint-Lambert, 1200, Belgium

We recently characterized system xc- (cystine/glutamate antiporter, xCT as specific subunit) as the major source of extracellular glutamate in the hippocampus/striatum by showing significantly decreased dialysate glutamate levels in system xc--deficient mice (xCT-/-) compared to wildtype littermates (xCT+/+). In order to exclude that this difference in glutamate levels is linked to compensatory changes in expression of the glutamate reuptake transporters (EAATs), we measured EAAT protein expression in hippocampal/striatal protein extracts of xCT-/- mice and wildtype littermates. No difference was observed. However, glutamate reuptake activity might be affected without changes in expression levels. Therefore, in this study, we conducted a D-[3H]-aspartate uptake assay on synaptosomes of different brain structures of the xCT-/- and xCT+/+ mice. Freshly dissected brain tissue was subjected to the assay that measures the activity of the EAATs by scintillation counting of the radioactive signal (expressed as pmol/min/mg protein). The specific values for the different EAATs were obtained by measuring the D-[3H]-aspartate uptake in the presence and absence of specific GLAST or GLT-1 inhibitors (WAY213613 and UCPH101). Our data show that there is no genotype-dependent effect on D-[3H]-aspartate uptake in prefrontal cortex, striatum and midbrain. On the other hand, we show that uptake of aspartate is significantly increased in the hippocampus and decreased in the spinal cord of xCT-/- versus xCT+/+ mice. Both changes are due to a change in activity of the GLT-1 transporter. These results contribute to the characterization of our transgenic model and will be subject for further research.
Originele taal-2English
TitelBelgian Society for Fundamental and Clinical Physiology and Pharmacology
StatusPublished - 2013

Vingerafdruk

Duik in de onderzoeksthema's van 'Glutamate uptake is affected in the central nervous system of system xc- deficient mice'. Samen vormen ze een unieke vingerafdruk.

Citeer dit