Analysis of structural plastic changes underlying L-DOPA induced dyskinesias in an animal model of parkinsonism.

TARAVINI IRE; SUÁREZ LM; GOMEZ G.; ESCANDE M; RELA L; MORATALLA R; MURER MG; GERSHANIK OS

Sydney

Congreso; 17th International Congress of Parkinson´s Disease and Movement Disorders.; 2013

Movement Disorder Society.

Objective: To analyze the structural modifications associated toL-DOPA induced dyskinesias (LID) in transgenic mice expressingfluorescent proteins under control of the D1 (striatonigral neurons) orD2 (striatopalidal neurons) receptor promoter by means of morphologicalanalysis of their dendritic trees.Background: L-DOPA remains the most efficacious drug for thetreatment of Parkinson?s disease despite it induces severe motorcomplications (dyskinesia). LID correlates with long-term functionalsynaptic changes in striatal neurons deprived of dopaminergic innervationsand once LID have been established they are rarelyreversible.Methods: Transgenic mice expressing red or green fluorescentmarkers in striatal neurons containing either the D1 or D2 receptorpromoter were injected with 6-OHDA in the mfb and treated withincreasing doses of L-DOPA (6, 12, 18 mg/kg). On fixed tissue sectionsstriatal neurons were iontophoretically injected with Luciferyellow and developed immunohistochemically using DAB as achromogen. Dendritic tree structure and density of dendritic spineswere analyzed using the Sholl Analysis with the ImageJ software(NIH) and Mercator Pro software to quantify the spines.Results: L-DOPA administration to mice having unilateral severeinjury of the nigrostriatal system dose-dependently induced LID. Preliminarydata show that 6-OHDA lesion led to reduced dendriticlength and spine density in both neuronal types. Conversely, a dyskinetogenicdose of L-DOPA led to spine regrowth differentiallyaffecting D1 and D2 striatal neurons.Conclusions: Our data suggest that a dyskinetogenic dose of LDOPAcould differentially modify the synaptic connectivity of eachneuronal type. We hope to further analyze if this striatal structuralchanges are directly related with the development of dyskinesias.