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01-04-2019 | Levodopa | Original Article

Differential Expression of Striatal ΔFosB mRNA and FosB mRNA After Different Levodopa Treatment Regimens in a Rat Model of Parkinson’s Disease

Authors: Victoria Palafox-Sanchez, Victoria Sosti, Gabriel Ramirez-García, Jaime Kulisevsky, José Aguilera, I. Daniel Limón

Published in: Neurotoxicity Research | Issue 3/2019

Abstract

Levodopa-induced dyskinesia (LID) is the main side effect associated with levodopa treatment and represents the biggest challenge for Parkinson’s disease therapy. While the overexpression of ΔFosB transcription factor is related to the development of LID, few studies have been undertaken on fosB gene transcriptional regulation induced by levodopa in vivo. The aim of this study is to evaluate the expression of ΔFosB mRNA and FosB mRNA in the striatum after acute, chronic, and subchronic levodopa treatment in rats with unilateral 6-OHDA-lesion in the medial forebrain bundle. qRT-PCR was used to compare the levels of ΔFosB and FosB mRNA expression in the dopamine-denervated striatum following levodopa treatment. While the results obtained after a single levodopa dose indicate a significant increase of ∆FosB mRNA expression in the striatum 1 h post-injection, the levels returned to baseline values after 24 h. After subchronic levodopa treatment, the levels of ∆FosB and FosB mRNA expression were lower 1 h post-administration of levodopa in comparison with acute effect. However, after chronic levodopa treatment, ∆FosB mRNA expression in the striatum persisted in dyskinetic rats only, and positive correlation was found between the levels of ∆FosB mRNA expression 1 h after levodopa administration and the level of dyskinetic severity. In summary, acute levodopa treatment led to highly increased levels of ∆FosB mRNA expression in the striatum. While repeated administration induced a partial desensitization of the fosB gene in the striatum, it did not suppress its activity completely, which could explain why dyskinesia appears after chronic levodopa treatment.

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Title: Differential Expression of Striatal ΔFosB mRNA and FosB mRNA After Different Levodopa Treatment Regimens in a Rat Model of Parkinson’s Disease
Authors: Victoria Palafox-Sanchez
Victoria Sosti
Gabriel Ramirez-García
Jaime Kulisevsky
José Aguilera
I. Daniel Limón
Publication date: 01-04-2019
Publisher: Springer US
Keywords: Levodopa
Parkinson's Disease
Published in: Neurotoxicity Research / Issue 3/2019
Print ISSN: 1029-8428
Electronic ISSN: 1476-3524
DOI: https://doi.org/10.1007/s12640-018-9993-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Differential Expression of Striatal ΔFosB mRNA and FosB mRNA After Different Levodopa Treatment Regimens in a Rat Model of Parkinson’s Disease

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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