Biphasic and bilateral changes in striatal VGLUT1 and 2 protein expression in hemi-Parkinson rats

Department of Pharmaceutical Chemistry and Drug Analysis, Research Group Experimental Pharmacology, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
Neurochemistry International (Impact Factor: 3.09). 05/2010; 57(2):111-8. DOI: 10.1016/j.neuint.2010.04.019
Source: PubMed


Parkinson's disease is characterized by disturbed glutamatergic neurotransmission in the striatum. Important mediators of extracellular glutamate levels are the vesicular glutamate transporters VGLUT1 and VGLUT2 in respectively corticostriatal and thalamostriatal afferents, next to the high-affinity Na(+)/K(+)-dependent glutamate transporters and the cystine/glutamate antiporter. In the present study, we compared bilateral striatal VGLUT1 and VGLUT2 protein expression as well as VGLUT1 and VGLUT2 transcript levels in the neocortex and parafascicular nucleus of hemi-Parkinson rats at different time intervals post unilateral 6-OHDA injection into the medial forebrain bundle versus controls. Three weeks post-injection we detected increased striatal VGLUT1 expression together with decreased VGLUT2 expression. On the other hand, after twelve weeks, the expression of VGLUT1 was decreased in hemi-Parkinson rats whereas the striatal expression of VGLUT2 was comparable to control rats. No effect could be seen on VGLUT transcript levels in the respective projection areas at any time. In conclusion, we observed a biphasic and bilateral change in the protein expression levels of both VGLUTs in the striatum of hemi-Parkinson rats indicative for a different and time-dependent change in glutamatergic neurotransmission from the two types of striatal afferents.

Download full-text


Available from: Lutgarde Arckens,
  • [Show abstract] [Hide abstract]
    ABSTRACT: The issue of cycle time reduction and its impact on a company's competitive edge has been gaining considerable attention recently. Generally speaking, shorter cycle times result in better customer satisfaction, lower work-in-process (WIP), higher yield, and better capacity given tool inventory and facility constraints. This paper provides a brief review of key concepts related to cycle time and describes a methodology for cycle time reduction projects in semiconductor wafer fabrication facilities, including the critically important implementation road map step. Finally, a case study is presented to illustrate the effectiveness and potential gains of the proposed cycle time reduction methodology
    Advanced Semiconductor Manufacturing Conference and Workshop, 1997. IEEE/SEMI; 10/1997
  • [Show abstract] [Hide abstract]
    ABSTRACT: Striatal dopamine loss in Parkinson's disease is accompanied by a dysregulation of corticostriatal glutamatergic neurotransmission. Within this study, we investigated striatal expression and activity of the glial high-affinity Na(+)/K(+)-dependent glutamate transporters, GLT-1 and GLAST, in the 6-hydroxydopamine hemi-Parkinson rat model at different time points after unilateral 6-hydroxydopamine injection into the medial forebrain bundle. Using semi-quantitative Western blotting and an ex vivo D-[(3)H]-aspartate uptake assay, we showed a time-dependent bilateral effect of unilateral 6-hydroxydopamine lesioning on the expression as well as activity of GLT-1. At 3 and 12 weeks post-lesion, striatal GLT-1 function was bilaterally upregulated whereas at 5 weeks there was no change. Even though our data do not allow a straightforward conclusion as for the role of glutamate transporters in the pathogenesis of the disease, they do clearly demonstrate a link between disturbed glutamatergic neurotransmission and glutamate transporter functioning in the striatum of a rat model for Parkinson's disease.
    Neurochemistry International 11/2010; 57(5):572-8. DOI:10.1016/j.neuint.2010.07.004 · 3.09 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Malfunctioning of system x(c)(-), responsible for exchanging intracellular glutamate for extracellular cystine, can cause oxidative stress and excitotoxicity, both important phenomena in the pathogenesis of Parkinson's disease (PD). We used mice lacking xCT (xCT(-/-) mice), the specific subunit of system x(c)(-), to investigate the involvement of this antiporter in PD. Although cystine that is imported via system x(c)(-) is reduced to cysteine, the rate-limiting substrate in the synthesis of glutathione, deletion of xCT did not result in decreased glutathione levels in striatum. Accordingly, no signs of increased oxidative stress could be observed in striatum or substantia nigra of xCT(-/-) mice. In sharp contrast to expectations, xCT(-/-) mice were less susceptible to 6-hydroxydopamine (6-OHDA)-induced neurodegeneration in the substantia nigra pars compacta compared to their age-matched wild-type littermates. This reduced sensitivity to a PD-inducing toxin might be related to the decrease of 70% in striatal extracellular glutamate levels that was observed in mice lacking xCT. The current data point toward system x(c)(-) as a possible target for the development of new pharmacotherapies for the treatment of PD and emphasize the need to continue the search for specific ligands for system x(c)(-).
    The FASEB Journal 12/2010; 25(4):1359-69. DOI:10.1096/fj.10-177212 · 5.04 Impact Factor
Show more