1. Differential gene expression induced by chronic levodopa treatment in the striatum of rats with lesions of the nigrostriatal system.
- Author
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Ferrario JE, Taravini IR, Mourlevat S, Stefano A, Delfino MA, Raisman-Vozari R, Murer MG, Ruberg M, and Gershanik O
- Subjects
- Animals, Behavior, Animal, Brain Diseases chemically induced, Calmodulin genetics, Calmodulin metabolism, Carrier Proteins genetics, Carrier Proteins metabolism, Cell Count methods, Corpus Striatum injuries, Cytokines genetics, Cytokines metabolism, Dopamine Plasma Membrane Transport Proteins, Female, Functional Laterality physiology, Gene Library, Immunohistochemistry methods, In Situ Hybridization methods, Membrane Glycoproteins metabolism, Membrane Transport Proteins metabolism, Myelin Basic Protein genetics, Myelin Basic Protein metabolism, Nerve Tissue Proteins metabolism, Oligonucleotide Array Sequence Analysis methods, Oxidopamine, Radioimmunoassay methods, Rats, Rats, Wistar, Antiparkinson Agents pharmacology, Brain Diseases metabolism, Corpus Striatum metabolism, Gene Expression drug effects, Levodopa pharmacology, Substantia Nigra metabolism
- Abstract
Levodopa, the major treatment for patients with Parkinson's disease, has been shown to induce a variety of compensatory effects, including facilitation of sprouting by dopaminergic neurons, in experimental animals with lesions leading to denervation of the striatum. To better understand the cellular and molecular environment where most of these compensatory changes take place, in particular elements that might contribute to the recovery of dopaminergic innervation, we have constructed a differential expression library enriched in transcripts from the striata of rats with lesions of the medial forebrain bundle treated with levodopa for 6 months. We have used this library to screen an expression array of rat genes representing the major cell functions, and have identified several that are involved in neurotrophic mechanisms and plasticity. We have confirmed the differential expression of selected transcripts by non-radioactive in situ hybridization, and report that the growth factor pleiotrophin, myelin basic protein and calmodulin are overexpressed in the denervated striatum of levodopa-treated rats.
- Published
- 2004
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