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GluR1 glutamate receptor subunit is regulated differentially in the primate basal ganglia following nigrostriatal dopamine denervation. Nigrostriatal dopaminergic denervation is associated with complex changes in the functional and neurochemical anatomy of the basal ganglia. The excitatory neurotransmitter glutamate mediates neural signaling at crucial points of this circuitry, and glutamate receptors are differentially distributed in the basal ganglia. Available evidence suggests that the glutamatergic corticostriatal and subthalamofugal pathways become overactive after nigrostriatal dopamine depletion. In this study, we have analyzed the regulation of the GluR1 subunit of the [-amino-3 -hydroxy-5 -methyl-4 -isoxazole] propionate glutamate receptor in the basal ganglia of primates following MPTP [1- methyl-4- phenyl-1,2,3,6- tetrahydropyridine] -induced dopamine denervation. The dopamine denervation resulted in distinct alterations in GluR1 distribution: (1) GluR1 protein expression was markedly increased in caudate and putamen, and this was most pronounced in the striosomes; (2) GluR1 protein was altered minimally in subthalamic nucleus; (3) expression of GluR1 was down-regulated in the globus pallidus by 63% and in the substantia nigra by 57%. The down-regulation of GluR1 expression in the output nuclei of the basal ganglia, the internal segment of the globus pallidus and the substantia nigra pars reticulata, may be a compensation for the overactive glutamatergic input from subthalamic nucleus, which arises after striatal dopamine denervation. Our results indicate that the glutamatergic system undergoes regulatory changes in response to altered basal ganglia activity in a primate model of Parkinson's disease. Targeted manipulation of the glutamatergic system may be a viable approach to the symptomatic treatment of Parkinson's disease. J Neurochem 2000 Mar;74(3):1166-74 Betarbet R, Porter RH, Greenamyre JT Department of Neurology, Emory University, Atlanta, Georgia 30322, USA. PMID: 10693949, UI: 20155616 http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=10693949&form=6&db=m&Dopt=b janet paterson 52 now / 41 dx / 37 onset a new voice: http://www.geocities.com/janet313/ 613 256 8340 PO Box 171 Almonte Ontario Canada K0A 1A0