Regulation of Pleiotrophin and Fyn in the striatum of rats undergoing L-DOPA-induced dyskinesia.

Autor: Gomez G; Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Junin 956, 1113, Buenos Aires, Argentina; CONICET - Universidad de Buenos Aires, Instituto de Investigaciones Farmacológicas (ININFA), Junin 956, 1113, Buenos Aires, Argentina., Saborido MD; Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Junin 956, 1113, Buenos Aires, Argentina; CONICET - Universidad de Buenos Aires, Instituto de Investigaciones Farmacológicas (ININFA), Junin 956, 1113, Buenos Aires, Argentina., Bernardi MA; Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Junin 956, 1113, Buenos Aires, Argentina; CONICET - Universidad de Buenos Aires, Instituto de Investigaciones Farmacológicas (ININFA), Junin 956, 1113, Buenos Aires, Argentina., Gershanik OS; Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Junin 956, 1113, Buenos Aires, Argentina; CONICET - Universidad de Buenos Aires, Instituto de Investigaciones Farmacológicas (ININFA), Junin 956, 1113, Buenos Aires, Argentina., Taravini IR; Laboratorio de Neurobiología Experimental, CONICET-Facultad de Bromatología, UNER, Presidente Perón 64, 2822, Gualeguaychú, Entre Ríos, Argentina., Ferrario JE; Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Junin 956, 1113, Buenos Aires, Argentina; CONICET - Universidad de Buenos Aires, Instituto de Investigaciones Farmacológicas (ININFA), Junin 956, 1113, Buenos Aires, Argentina. Electronic address: ferrario@ffyb.uba.ar.
Jazyk: angličtina
Zdroj: Neuroscience letters [Neurosci Lett] 2018 Feb 14; Vol. 666, pp. 5-10. Date of Electronic Publication: 2017 Dec 11.
DOI: 10.1016/j.neulet.2017.12.024
Abstrakt: 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.
(Copyright © 2017 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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