Time-dependent changes in GLT-1 functioning in striatum of hemi-Parkinson rats.
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.
Massie
Ann
A
Department of Pharmaceutical Chemistry and Drug Analysis, Vrije Universiteit Brussel, Brussels, Belgium.
Goursaud
Stéphanie
S
Schallier
Anneleen
A
Vermoesen
Katia
K
Meshul
Charles K
CK
Hermans
Emmanuel
E
Michotte
Yvette
Y
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000378:metabolism / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism; D027341:Excitatory Amino Acid Transporter 1 / Q000096:biosynthesis / Q000235:genetics; D027342:Excitatory Amino Acid Transporter 2 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry; D008474:Medial Forebrain Bundle / Q000378:metabolism / Q000502:physiology; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000503:physiopathology*; D010879:Piperazines / Q000378:metabolism; D051381:Rats; D013574:Synaptosomes / Q000378:metabolism; D013997:Time Factors
D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D010879:Piperazines; C493395:Slc1a2 protein, rat; C493392:Slc1a3 protein, rat; D001224:Aspartic Acid; D016627:Oxidopamine; C044630:1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine; D004298:Dopamine