Differential gene expression induced by chronic levodopa treatment in the striatum of rats with lesions of the nigrostriatal system.

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.

Effects of orally administered levodopa on mesencephalic dopaminergic neurons undergoing a degenerative process.

Although the issue of in vivo levodopa toxicity appears to be settled by now in the light of recent findings, a crucial aspect was not accounted for the experiments designed to tackle that question. Levodopa could in fact be non-toxic on surviving dopamine neurons, but that could not be the case when the drug is administered at the same time those neurons are undergoing degeneration, which is what happens in the clinical setting. Dopaminergic neurons could in that situation be more vulnerable to levodopa's potential toxic action.