CHANGES IN GENE EXPRESSION IN STRIATUM OF 6-OHDA LESIONED RATS INDUCED BY LONG TERM ORAL LEVODOPA TREATEMENT: A CLUE FOR PLASTICTY AND DYSKINESIAS.

FERRARIO, JUAN ESTEBAN; MOURLEVAT, SOPHIE; DELFINO, MARINA; STEFANO, ANDREA; RAISMAN-VOZARI, RITA; GERSHANIK, OSCAR; MURER, GUSTAVO; RUBERG, MERLE

San Diego, USA

Congreso; Society for Neuroscience Meeting; 2001

Society for Neuroscience

Levodopa therapy is the most widely used treatment for Parkinson’s Disease (PD). In addition to its potent therapeutic activity, several undesired side-effects may appear after several years of treatment. Levodopa has also been suspected to be toxic to dopaminergic neurones, although this has been disproved. On the contrary, it has been reported that, under certain conditions, levodopa promotes neurite outgrowth (Mena et al, l997) and plasticity (Murer et al, 1998). The undesired effects of this drug and its trophic properties may result from induction of gene expression. To approach this issue, we have given levodopa/carbidopa orally for 6 month (170/70 mg/Kg/day) to female rats unilaterally lesioned with 6-OHDA and have prepared a cDNA library enriched in transcripts differentially expressed in the ipsilateral striatum of levodopa-treated rats by subtraction with transcripts from untreated animals. Hybridization of the subtracted library with probes from striatal cDNA of untreated animals showed that only 5% were common to both. The subtracted cDNA were screened by hybridization to a rat gene microarray. Only 58 genes of 1176 in the array were labelled, among which SOD1, myelin basic protein, TGF-beta II receptor, insulin receptor, prolactin like protein A. These results show that important changes in gene regulation occur after long-term levodopa treatment, and give clues as to how these changes might modify the natural history of PD.