OBJECTIVES: Studying expression levels, using semi-quantitative Western blotting, of VGLUT1, GLAST, GLT-1 and xCT, the specific subunit of the cystine/glutamate antiporter, in striatum of rats at different survival times (3, 5 and 12 weeks) after unilateral 6-OHDA injection into the medial forebrain bundle. BACKGROUND: It is common knowledge that main mediators in the pathogenesis of Parkinson's disease are oxidative stress, excitotoxicity and mitochondrial dysfunction. Increased glutamate concentrations can be linked 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. RESULTS: xCT is the only protein that shows differences in expression between striata of both hemispheres of unilaterally 6-OHDA injected rats, 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 lesioned rats compared to 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). CONCLUSION: Given earlier observations by Meshul et al. (1999) of biphasic changes in extracellular glutamate after 6-OHDA lesioning, with increases 1 month post-lesion and decreases 3 months post-lesion, our data suggest an important role of xCT and VGLUT1 in determining the aberrant extracellular glutamate levels in the 6-OHDA rat model. Modulation of these transporters might help to normalize extracellular glutamate levels and prevent further excitotoxic and oxidative damage.
Original languageEnglish
Title of host publicationBelgian Brain Congress 2008
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

ID: 1749677