Analysis of structural plastic changes underling L-DOPA induced dyskinesias in an animal model of Parkinson's disease

GÓMEZ G; LARRAMENDY C; SABORIDO MD; ESCANDE M; BELFORTE J; MURER MG; GERSHANIK OS; TARAVINI IR

Córdoba

Congreso; XXVI Congreso Anual de la SAN; 2011

Sociedad Argentina de Investigación en Neurociencias (SAN)

L-DOPA remains most efficacious drug for the treatment of Parkinson?s disease despite it induces severe motor complications (dyskinesia). L-DOPA-induced dyskinesias (LID) are correlated with post-synaptic plastic changes in D1 pathway striatal neurons deprived of DAergic innervation. It is well known that L-DOPA induces persistent molecular and that LID are rarely reversible. Our current hypothesis is that striatal structural changes imply an increase of the D1 pathway synaptic connectivity. To test it, we developed an animal model of LID in transgenic mice expressing red or green fluorescent markers under control of the D1 (striatonigral neurons) or D2 (striatopalidal neurons) receptor promoter, respectively. Mice were injected with 6- hydroxydopamine in the medial forebrain bundle and treated with increasing doses of L-DOPA. As expected we found a dose-dependent induction of LID. In these animals we are analyzing the structural modifications in each neuronal type by means of morphological analysis of their dendritic trees. We expect that this work will allow a broad comprehension about the structural changes that take place in the striatum as a consequence of L-DOPA treatment and its relation with the development of dyskinesias.