Unravelling the molecular role of Fyn in levodopa induced dyskinesia (LID)

BORDONE M; BERNARDI MA; DAMIANICH A; SANZ BLASCO S; GOMEZ G; TARAVINI I; AVALE E; GERSHANIK OS; FERRARIO JE

Buenos Aires

Congreso; 2nd FALAN Congress; 2016

FALAN (Federation of Latin American and Caribbean Neuroscience Societies)

In order to control the development of LID in PD therapyit is necessary to understand the molecular changesthat take place in the striatum. We have previouslyexplored the pathway Pleiotrophin/RPTPζ/b/Fyn, whichis altered as a consequence of dopaminergic cell loss andL-DOPA treatment. RPTP /b interacts with PSD95 at thepostsynaptic density complex and regulates the amountof Fyn kinase phosphorylation The aim of this work wasto study the crosstalk between D1 receptor (D1R) and thesignaling of Fyn protein kinase in a mice model of L-DOPAinduced dyskinesias (LID). For this goal, we reproducedthe model of LID both in Fyn knock-out (KO) and wildtype (WT) mice. Dopaminergic fibers were damaged withunilateral injection of 6-OHDA and mice were treated dailywith L-DOPA for 2 weeks. Additional experimental groupswere used as control for surgery, treatment and lesion.We performed behavioral tests to determine abnormalinvoluntary movements (AIMs). Dopaminergic denervationwas confirmed by immunodetection of TH in the SNpc.Molecular markers of LID (ΔFosB, pERK), TH and otherproteins were determined by Western blot. Fyn-KO micedisplayed lower levels of AIMs than WT littermates. We havereproduced previously reported changes in the regulationof LID markers on WT mice, while the lower level of LIDs in Fyn-KO mice appears to be associated to a downregulationof the transcription factor ΔFosB