Levodopa treatment induces changes in the expression of Pleiotrophin receptors in a rat model of Parkinson’s disease.

FERRARIO, JUAN ESTEBAN; SALDAÑA-ORTEGA, MARISA; TARAVINI, IRENE; MURER, GUSTAVO; HUNOT, STEPHANE; GERSHANIK, OSCAR; RAISMAN-VOZARI, RITA

Tokyo, Japon

Congreso; 10th international congress of Parkinson's Disease and Movement Disorders; 2006

Movement Disorders Society

Parkinson’s disease (PD) is characterized by selective damage to the dopaminergic nigrostriatal pathway. Surviving neurons undergo both spontaneous and levodopa induced plastic changes. We have recently identified pleiotrophin (PTN) mRNA as being increased in the lesioned striatum of hemiparkinsonian rats after a long term treatment with levodopa. In addition, it has been shown that PTN enhances the maturation of dopaminergic neurons in vitro. This data, among others, suggest that PTN may be a new modulatory factor for dopaminergic neurons, and consequently, may contribute to the plastic adaptations aimed at restoring dopaminergic neurotransmission in the damaged striatum. Thus, the PTN receptors involved in this function might represent a crucial pharmacological target in the treatment of PD. The  intracellular effects of PTN are mediated by three known membrane receptors: N-syndecan, RPTP z/beta and ALK. Abundant evidence suggests that RPTPz/beta mediates the differentiation and axonal growth attributed to PTN. To go beyond our previous observations in vivo, we analyzed the changes in expression of PTN and its receptors in the dopaminergic system, by quantitative real time RT-PCR on total RNA purified from the ventral mesencephalon of rats lesioned with intrastriatal 6-OHDA, which were treated either with vehicle or levodopa for 21 days. We found that RPTPz/beta mRNA is upregulated in the mesencephalon of 6-OHDA rats treated with levodopa compared to both the untreated and non-lesioned groups. We used the method of 2-delta/delta Ct to relative quantify the data which were normalized using G3PDH as a reference gene. It is, therefore, tempting to speculate that RPTPz/beta may be the receptor that mediates the effect of PTN on dopaminergic neurons, and contribute to the recovery observed after levodopa treatment. Further work is under way to verify this hypothesis.