RESUMO

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.

Assuntos

Antiparkinsonianos/farmacologia , Encefalopatias/metabolismo , Corpo Estriado/metabolismo , Expressão Gênica/efeitos dos fármacos , Levodopa/farmacologia , Substância Negra/metabolismo , Animais , Comportamento Animal , Encefalopatias/induzido quimicamente , Calmodulina/genética , Calmodulina/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Contagem de Células/métodos , Corpo Estriado/lesões , Citocinas/genética , Citocinas/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina , Feminino , Lateralidade Funcional/fisiologia , Biblioteca Gênica , Imuno-Histoquímica/métodos , Hibridização In Situ/métodos , Glicoproteínas de Membrana/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Proteína Básica da Mielina/genética , Proteína Básica da Mielina/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Oxidopamina , Radioimunoensaio/métodos , Ratos , Ratos Wistar