The kinase Fyn has an important role in NMDA receptor regulation in L-DOPA induced dyskinesia in a mouse model of Parkinson?s disease

OSCAR GERSHANIK; GIMENA GOMEZ; MELINA BORDONE; JUAN FERRARIO; IRENE TARAVIN; ANA DAMIANICH; LUCIANA ISAJA; ELENA AVALE; ALEJANDRA BERNARDI; SANZ BLASCO S

Mar del Plata

Congreso; XXXII Congreso SAN 2017; 2017

Sociedad Argentina de Neurociencias

Levodopa (L-DOPA) induced dyskinesia (LID) is a side effect of Parkinson?s disease (PD)treatment. A great challenge is to reduce the development of LID without affecting therestorative effect of dopamine stimulation. It has been established that DA stimulationincreases the phosphorylation at tyrosine 1472 of NR2B, regulatory subunit of NMDAR, whichis one target of the Src kinase Fyn. Our aim is to address the role of Fyn in the NMDARactivation under L-DOPA stimulation in a mouse model of PD and the role of Fyn in thegenesis of LID. We developed a model of PD in Fyn-KO and WT mice by induction ofdopaminergic death by means of unilateral injection of 6-OHDA, and mice induced todeveloped LID by daily treatment with L-DOPA. Dopaminergic denervation was confirmed byimmunodetection of TH in the SN. ΔFosB, TH, pNR2B were determined in the striatum byWB.Fyn-KO mice show a significant reduction in NR2B phosphorylation concomitant with a LIDreduction, as shown by behavioural tests and ΔFosB levels reduction. In an independent setof experiments, WT mice were injected with 6-OHDA and randomly assigned to receiveAmantadine (NMDA receptor antagonist), Saracatinib (Src kinase inhibitor), both, or vehicletogether with L-DOPA. The three groups were compared in their ability to develop LID andthe expression of molecular markers of LID.