Project l of the UCLA Center for the Study of Parkinson's Disease will use quantitative molecular and anatomical techniques to address the central hypothesis of the Center: loss of nigrostriatal neurons, as well as both pharmacological and surgical treatments of Parkinson's disease, alter the molecular and cellular characteristics o neurons of the subthalamic nucleus. Levels and pattern of expression of mRNAs encoding subtypes/subunits of glutamatergic. OABAergic and dopaminergic receptors will be examined in the subthalamic nucleus and its target areas with Polymerase Chain Reaction (PCR) and in situ hybridization histochemistry. This analysis will be extended to genes involved in signal transduction and regulation of these receptors after identification of alterations in the expression of candidate genes with DNA microarray technology in Core C. The following animal models will be generated in Core B and examined in this project: l) rats with nigrostriatal lesions; 2) rats with lesions treated with L-DOPA; 3) rats with lesions and chronic deep brain stimulation of the subthalamic nucleus; 4) rats with lesions and transplants of GABA-producing cells in the subthalamic nucleus. Salient findings will be examined in post-mortem human brain collected as part of CoreB. The data obtained in this project will provide the molecular informatioji necessary for the interpretation of in vitro electrophysioiogical experiments performed in project 2 and in vivo microdialysis and behavioral experiments performed in project 3 on the same animal models.
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