Exploring Fyn as a novel molecule in Levodopa induced dyskinesias

BORDONE, MELINA; SANZ-BLASCO, SARA; DAMIANICH, ANA; BERNARDI, ALEJANDRA; AVALE, MARIA ELENA; SABORIDO, MARIANO; GOMEZ, GIMENA; TARAVINI, IRENE; GERSHANIK, OSCAR; FERRARIO, JUAN ESTEBAN

Mar del Plata

Congreso; XXX SAN Annual meeting; 2015

Sociedad Argentina de Investigaciones en Neurociencias

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). To control LID in PD therapy is necessary to better understand the multiple cellular and molecular changes that take place during LID. Some protein and gene changes have been reported within the dyskinetic striatum, but the mechanisms in which they are involved are not fully understood. Pleiotrophin and its receptor RPTPz/b are up-regulated as a consequence of dopaminergic cell loss and L-DOPA treatment. RPTPz/b interacts with PSD95 at the postsynaptic density complex and regulates the protein kinase Fyn, a key molecule involved in synaptic plasticity andcytoskeleton stability. We found an increase in the number of Pleiotrophin(+) neurons and that Fyn is highly phosphorylated in the striatum of dyskinetic rats. We performed behavioral tests and determined abnormal involuntary movements (AIMs) in a model of LID in both Fyn knock-out (KO) and WT mice. Dopaminergic denervation was confirmed by immunodetection of nigral and striatal tyrosine hydroxylase. In addition, the levels of molecular markers involved in LID were determined by Western blot. Fyn KO mice showed a significant reduction in the development of AIMs in relation to WT controls. Our data suggest that Fyn might be involved in the development of LID, and its role as a potential target to control AIMs.