Evaluation of strategic genes reinforce the idea that trophic events take place in the striatum of levodopa-treated parkinsonian rats

FERRARIO JE; TARAVINI IR; DELFINO MA; STEFANO A; MOURLEVAT S; RUBERG M; RAISMAN-VOZARI R; MURER MG; GERSHANIK O

New Orleans, Louisiana, USA

Congreso; 33rd Annual Meeting of Society for Neuroscience; 2003

Society for Neuroscience

Levodopa therapy is the universally used treatment of Parkinson’s Disease because of its unparalleled potency. However, many patients develop debilitating undesired effects after several years of treatment. It has been reported that under certain conditions levodopa promotes dopamine neuron plasticity (Mena et al., 1997; Murer et al, 1998). Levodopa-induced plasticity may be related to its therapeutic actions and undesired effects. We have constructed a differential expression library enriched in transcripts from the striata of rats bearing nigrostriatal lesions treated with levodopa for 6 month, and screened a large number of genes, including some related to mechanisms of protection against oxidative stress and plasticity/trophism. The aim of this study were: i) to confirm the differential expression of the most relevant genes in an independent group of treated rats; ii) to characterize the regional and cellular expression patterns of these genes. We analyzed the expression of selected genes by non radioactive in situ hybridization and found that pleiotrophin (also expressed during development and wound repair) and myelin basic protein (a key molecule in neuronal reconstruction) are over-expressed, among others, in the striatum of levodopa-treated rats. Moreover, the overall analysis of our results (previous and recent ones) taken together with other related reports, reinforce the hypothesis that trophic events occur in the partially-denervated striatum as a consequence of long term levodopa treatment. Even though functional evidence regarding the role of the library transcripts in levodopa-induced dopamine neuron plasticity is still lacking, the levodopa-induced overexpression of trophhic factors and related molecules merits further attention.