Objective
One of the mediators of neurodegeneration in Parkinson's disease is glutamate excitotoxicity. Increased activity of the subthalamic nucleus has been observed in animal models and may result in increased glutamate release in substantia nigra pars reticulata (SNr). Since extracellular glutamate concentrations are determined by glutamate reuptake from the extracellular space, we studied expression and activity of the glial glutamate transporters, GLAST and GLT-1, in SNr and striatum of hemi-Parkinson rats with 6-hydroxydopamine (6-OHDA) medial forebrain bundle lesions, at different times post-lesion.

Methods
We used Western blotting to study the expression levels of GLAST and GLT-1. To investigate whether a change in expression level is linked to a change in glutamate reuptake activity, we performed in vivo microdialysis experiments during which we perfused the probe with L-trans-pyrrolidine-3,4-dicarboxylate (L-PDC, 1mM) or dihydrokainate (DHK, 1mM), two inhibitors of the glutamate transporters.

Results
For both transporters we observed differences in expression level between SNr of the lesioned and non-lesioned side of the hemi-Parkinson rat, depending on the survival time after lesioning. In the striatum no significant differences could be detected between both hemispheres. In both nuclei there was a difference between the expression level of both transporters between the non-lesioned hemisphere of the hemi-Parkinson rat and a control animal. As for the reuptake activity, we measured in both nuclei of control animals increases in extracellular glutamate concentrations of approximately 1000% and 250% when using respectively L-PDC and DHK. The increase in extracellular glutamate concentration reflects the reuptake activity for glutamate and will be compared between hemi-Parkinson and control rats.

Discussion
Our data are indicative for complex changes at the level of the glial glutamate transporters as a function of time after lesioning, in the 6-OHDA rat model. Further experiments will reveal whether these changes are the result of or the reason for neurodegeneration observed during Parkinson's disease.
Original languageEnglish
Title of host publicationParkinsonism & Related Disorders
Pages126-127
Number of pages1
Volume13
Publication statusPublished - 2007
EventFinds and Results from the Swedish Cyprus Expedition: A Gender Perspective at the Medelhavsmuseet - Stockholm, Sweden
Duration: 21 Sep 200925 Sep 2009

Publication series

NameParkinsonism & Related Disorders

Conference

ConferenceFinds and Results from the Swedish Cyprus Expedition: A Gender Perspective at the Medelhavsmuseet
CountrySweden
CityStockholm
Period21/09/0925/09/09

    Research areas

  • Parkinson's disease, nuclei basal ganglia, glutamate transport

ID: 1749429