Regulation of Pleiotrophin and Fyn in the striatum of rats undergoing L-DOPA-induced dyskinesia
| Autor: | Mariano D. Saborido, Oscar S. Gershanik, Juan E. Ferrario, Gimena Gomez, Irene R. E. Taravini, M. Alejandra Bernardi |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Dyskinesia Drug-Induced CIENCIAS MÉDICAS Y DE LA SALUD Parkinson's disease Dopamine L-DOPA Inmunología Striatum Proto-Oncogene Proteins c-fyn Medium spiny neuron Pleiotrophin Receptors N-Methyl-D-Aspartate Molecular mechanism Levodopa Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine FYN Fyn medicine Animals Neurons Dyskinesia Chemistry General Neuroscience Parkinson Disease Corpus Striatum Cell biology Medicina Básica Disease Models Animal 030104 developmental biology nervous system Cytokines Carrier Proteins Postsynaptic density Tyrosine kinase 030217 neurology & neurosurgery medicine.drug Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Neuroscience Letters. 666:5-10 |
| ISSN: | 0304-3940 |
| DOI: | 10.1016/j.neulet.2017.12.024 |
| Popis: | L-DOPA is the gold standard pharmacological therapy for symptomatic treatment of Parkinson´s disease (PD), however, its long-term use is associated with the emergence of L-DOPA-induced dyskinesia (LID). Understanding the underlying molecular mechanisms of LID is crucial for the development of newer and more effective therapeutic approaches. In previous publications, we have shown that Pleiotrophin (PTN), a developmentally regulated trophic factor, is up-regulated by L-DOPA in the striatum of dopamine denervated rats. We have also shown that both mRNA and protein levels of RPTPζ/β, a PTN receptor, were upregulated in the same experimental condition and expressed in striatal medium spiny neurons. The PTN-RPTPζ/β intracellular pathway has not been fully explored and it might be implicated in the striatal plastic changes triggered by L-DOPA treatment. RPTPζ/β is part of the postsynaptic density zone and modulates Fyn, a Src tyrosine kinase that regulates the NR2A and NR2B subunits of the NMDA receptor and has been singled out as a key molecule in the development of LID. In this study, we evaluated the changes in PTN and Fyn protein levels and Fyn phosphorylation status in the 6-OHDA rat model of PD rendered dyskinetic with L-DOPA. We found an increase in the number of PTN immunoreactive neurons, no changes in the amount of total Fyn but a significant increase in Fyn phosphorylation in the dorsolateral striatum of dyskinetic rats. Our results support the idea that both PTN and Fyn may be involved in the development of LID, further contributing to the understanding of its molecular mechanisms. Fil: Gomez, Gimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina Fil: Saborido, Mariano Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina Fil: Bernardi, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina Fil: Gershanik, Oscar Samuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina Fil: Taravini, Irene Rita Eloisa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Entre Ríos. Facultad de Bromatología; Argentina Fil: Ferrario, Juan Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina |
| Databáze: | OpenAIRE |
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