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

BERNARDI A; GOMEZ G; GERSHANIK O; BORDONE M; SANZ-BLASCO S; AVALE E; DAMIANICH A; TARAVINI I

Buenos Aires

Congreso; 2nd FALAN Congress; 2016

Federation of Latin American and Caribbean Neuroscience Societies (FALAN) y Sociedad Argentina de Investigación en Neurociencias (SAN)

In order to control the development of LID in PD therapy it is necessary to understand the molecular changes that take place in the striatum. We have previously explored the pathway Pleiotrophin/RPTP ζ/b/Fyn, which is altered as a consequence of dopaminergic cell loss and L-DOPA treatment. RPTPζ/b interacts with PSD95 at the postsynaptic density complex and regulates the amount of Fyn kinase phosphorylation The aim of this work was to study the crosstalk between D1 receptor (D1R) and the signaling of Fyn protein kinase in a mice model of L-DOPA induced dyskinesias (LID). For this goal, we reproduced the model of LID both in Fyn knock-out (KO) and wild type (WT) mice. Dopaminergic fibers were damaged with unilateral injection of 6-OHDA and mice were treated daily with L-DOPA for 2 weeks. Additional experimental groups were used as control for surgery, treatment and lesion. We performed behavioral tests to determine abnormal involuntary movements (AIMs). Dopaminergic denervation was confirmed by immunodetection of TH in the SNpc. Molecular markers of LID (ΔFosB, pERK), TH and other proteins were determined by Western blot. Fyn-KO mice displayed lower levels of AIMs than WT littermates. We have reproduced previously reported changes in the regulation of LID markers on WT mice, while the lower level of LIDs in Fyn-KO mice appears to be associated to a downregulation of the transcription factor ΔFosB.