Exploring a novel pathway in Levodopa induced dyskinesia

CAMPANA S; SABORIDO MD; AVALE E; GOMEZ G; TARAVINI IRE; HANGER D; GERSHANIK OS; FERRARIO JE

Córdoba

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

Sociedad Argentina de Investigación en Neurociencia

Parkinsons disease (PD) is a neurodegenerative disorder which results from theselective death of nigroestrial dopaminergic neurons. The administration of LDOPAis the most effective symptomatic pharmacological therapy. Despite of itsbenefits, 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 goalit is necessary to better comprehend the multiple cellular and molecularmechanisms that take place during LID. Although some protein and gene changeshave been described into the dyskinetic striatum, the functions and/or mechanismon which they are involved are not fully understood . In our laboratory we haveshown that Pleiotrophin and its receptor RPTPz/b are upregulated as aconsequence of dopaminergic loss and L-DOPA treatment. RPTPz/b belongs to thepost synapsis density complex, where it interacts with PSD95 and regulates theprotein kinase Fyn. Several evidences point Fyn as a potential candidate involvedin LID. To test this hypothesis, we have analyzed the amount of Fyn protein and itsphosphorylation state in the striatum of dyskinetic rats. We have also developed aLID model in Fyn KO mice. We found that Fyn is highly phosphorilated in dyskineticstriata while Fyn KO mice show less dyskinesia than wt controls. Our evidencessupport a role of Fyn in LID, yet further work is still necessary to determine themechanism on which it may be involved.