Exploring a novel pathway in Levodopa induced dyskinesia.

CAMPANA, SOLEDAD; SABORIDO, MARIANO; AVALE, MARIA ELENA; GOMEZ, GIMENA; TARAVINI, IRENE; HANGER, DIANE; GERSHANIK, OSCAR; FERRARIO, JUAN ESTEBAN

Huerta Grande, Cordoba

Congreso; XXVIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencia.; 2013

Parkinson´s disease (PD) is a neurodegenerative disorder which results from the selective death of nigroestrial dopaminergic neurons. The administration of L-DOPA is the most effective symptomatic pharmacological therapy. Despite of its benefits, most patients develop side effects known as L-DOPA induced dyskinesias (LID). The current great challenge in PD therapy is to control LID. To reach this goal it is necessary to better comprehend the multiple cellular and molecular mechanisms that take place during LID. Although some protein and gene changes have been described into the dyskinetic striatum, the functions and/or mechanism on which they are involved are not fully understood . In our laboratory we have shown that Pleiotrophin and its receptor RPTPz/b are upregulated as a consequence of dopaminergic loss and L-DOPA treatment. RPTPz/b belongs to the post synapsis density complex, where it interacts with PSD95 and regulates the protein kinase Fyn. Several evidences point Fyn as a potential candidate involved in LID. To test this hypothesis, we have analyzed the amount of Fyn protein and its phosphorylation state in the striatum of dyskinetic rats. We have also developed a LID model in Fyn KO mice. We found that Fyn is highly phosphorilated in dyskinetic striata while Fyn KO mice show less dyskinesia than wt controls. Our evidences support a role of Fyn in LID, yet further work is still necessary to determine the mechanism on which it may be involved.