Exploring Fyn as a novel molecule in Levodopa induced dyskinesias

SANZ-BLASCO, SARA; AVALE, MARIA ELENA; CAMPANA, SOLEDAD; DAMIANICH, ANA; SABORIDO, MARIANO; GOMEZ, GIMENA; TARAVINI, IRENE; GERSHANIK, OSCAR; FERRARIO, JUAN ESTEBAN

San Diego, California

Congreso; 19th International Congress of Parkinson?s Disease and Movement Disorders; 2015

Movement Disorders Society

The administration of L-DOPA is the most effective symptomatic pharmacological therapy for Parkinson´s disease (PD). Despite its benefits, most patients develop side effects known as L-DOPA induced dyskinesias (LID). One of the current great challenges in PD therapy is to control LID. To reach this goal it is necessary to better understand the multiple cellular and molecular mechanisms that take place during LID. Although some protein and gene changes have been described within the dyskinetic striatum, the functions and/or mechanism in 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 cell loss and L-DOPA treatment. RPTPz/b belongs to the post synaptic density complex, where it interacts with PSD95 and regulates the protein kinase Fyn, a key molecule in postsynaptic signaling and reorganization. Several evidences suggest Fyn as a potential candidate involved in LID. Methods: We have determined the amount of Pleiotrophin immunopositive neurons and analyzed the amount of Fyn protein and its phosphorylation state by western blot in striata of dyskinetic rats. Also, we have developed the model of LID in both Fyn knock-out (KO) and WT mice, in which we have performed behavioral tests, determined abnormal involuntary movements (AIMs) and performed histological determinations such as tyrosine hydroxylase and FosB/ΔFosB. Results: We found that the number of PTN positive neurons is increased and that Fyn is highly phosphorylated in the striatum of dyskinetic rats, while Fyn KO mice show a significant reduction in the development of AIMs in comparison to WT controls. Conclusions: Our data suggest that Fyn might be involved in the development of LID, yet further work is still necessary to determine the mechanism in which it may be involved and if it could be targeted to control LID.