INVESTIGADORES
TARAVINI Irene Rita Eloisa
congresos y reuniones científicas
Título:
Analysis of structural plastic changes underlying L-DOPA induced dyskinesias in an animal model of Parkinson's disease
Autor/es:
TARAVINI I; SUÁREZ LM; GÓMEZ G; LARRAMENDY C; SABORIDO MD; ESCANDE M; BELFORTE J; RELA L; MORATALLA R; MURER GM; GERSHANIK O
Lugar:
Buenos Aires
Reunión:
Conferencia; 5th Special Conference of the International Society for Neurochemistry. ?Synapses and dendritic spines in health and disease?; 2012
Institución organizadora:
The International Society for Neurochemistry
Resumen:
Parkinson´s
disease is a neurodegenerative disorder characterized by a gradual loss of
dopaminergic neurons in the substantia nigra pars compacta, leading to a
progressive reduction of dopamine levels in the striatum. L-DOPA remains the most
efficacious treatment despite inducing severe motor complications (dyskinesia). L-DOPA-induced
dyskinesias (LID) correlate with post-synaptic plastic changes in striatal
neurons deprived of dopaminergic innervations. Once LID have been established they
are rarely reversible. Our current hypothesis is that striatal structural
changes involve an increase in synaptic connectivity of the D1 pathway. We have
the following aims: (I) To
develop an animal model of LID in transgenic mice expressing fluorescent proteins
under control of the D1 (striatonigral neurons) or D2 (striatopalidal neurons)
receptor promoter. (II) To analyze the structural modifications after L-DOPA
treatment in each neuronal type by means of morphological analysis of their
dendritic trees. Transgenic mice expressing red or green fluorescent markers in
striatal neurons containing either the D1 or D2 receptor promoter were
injected with 6-hydroxydopamine in the medial forebrain bundle and
treated with increasing doses of L-DOPA (6, 12, 18 mg/kg). Fixed tissue
sections from the striatum were obtained and striatal neurons were iontophoretically
injected with Lucifer yellow. These cells were revealed immunohistochemically
using DAB as a chromogen. To analyze the dendritic tree structure and the density of dendritic spines we used the NIH software ImageJ to perform the Sholl
Analysis and Mercator Pro software to quantify the spines. We
induced a unilateral severe injury of the nigrostriatal system in mice by
injection of 6-hydroxydopamine and designed a protocol of L-DOPA administration
that successfully induced a dyskinetic phenomenon. As expected we found a
dose-dependent development of LID. Additionally, we have performed the first
experiments of Lucifer yellow iontophoretic injections of striatal neurons. At
present, we are analyzing if dyskinetogenic doses of L-DOPA can modify the
synaptic connectivity of each neuronal type. Evaluation of dendritic tree
morphology and dendritic spine number and shape is in progress.