It is common knowledge that the main mediators in the pathogenesis of Parkinson's disease are oxidative stress, excitotoxicity and mitochondrial dysfunction. Increased glutamate concentrations can be linked, directly or indirectly, to all of these processes. Extracellular glutamate concentrations are determined by an interplay between vesicular glutamate transporters (VGLUTs), glial high-affinity Na+/K+-dependent glutamate transporters (GLAST and GLT-1) and the cystine/glutamate antiporter. Using semi-quantitative Western blotting, we studied the expression levels of VGLUT1, GLAST, GLT-1 and xCT, the specific subunit of the cystine/glutamate antiporter, in the striatum of rats at different survival times (3, 5 and 12 weeks) after unilateral 6-OHDA injection into the medial forebrain bundle. xCT is the only protein that shows differences in expression between striata of both hemispheres of a unilaterally 6-OHDA injected rat, with higher expression levels in the lesioned compared to intact hemisphere 3 weeks after lesion. For all other transporter proteins, i.e. GLT-1, GLAST and VGLUT1, the main differences in expression levels were observed bilaterally, i.e. in left and right striatum of a lesioned rat compared to the striatum of control rats. Expression levels of GLT-1 and VGLUT1 were significantly increased 3 weeks post-lesion. On the other hand, 12 weeks post-lesion, the striatal expression levels of VGLUT1 and GLAST were significantly decreased whereas those of GLT-1 were increased. For all glutamate transporters, 5 weeks post-lesion seems to be a transition period during which expression levels were decreased (GLT-1, xCT) or unchanged (VGLUT1, GLAST). Given earlier observations by Meshul et al. (1999) of a biphasic change in extracellular glutamate levels after 6-OHDA lesioning, with increases 1 month post-lesion and decreases 3 months post-lesion, our data are suggestive of an important role of xCT and VGLUT1 in determining the aberrant extracellular glutamate levels in the 6-OHDA rat model. Modulation of one or more of these transporters might help to normalize the extracellular glutamate levels and prevent further excitotoxic and oxidative damage.
Original languageEnglish
Title of host publication38th Annual Meeting for the Society of Neuroscience
Publication statusPublished - 2008
EventFinds and Results from the Swedish Cyprus Expedition: A Gender Perspective at the Medelhavsmuseet - Stockholm, Sweden
Duration: 21 Sep 200925 Sep 2009

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, glutamate transport, striatum

ID: 1748926