Differential Expression of Striatal ΔFosB mRNA and FosB mRNA After Different Levodopa Treatment Regimens in a Rat Model of Parkinson’s Disease
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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.
KeywordsΔFosB mRNA Levodopa Dyskinesia fosB gene Striatum
abnormal involuntary movements
immediate early genes
medial forebrain bundle
messenger ribonucleic acid
medium-sized spiny neurons
Thanks to Benjamin Stewart (English language native and academic proofreader) for editing the English language text.
This research was partially supported by CONACyT-Mexico Grant 169023, VIEP-BUAP 2018-2019 awarded to I.D. Limón, and Grant SAF2013 43900, awarded by the Spanish Ministry of Economics and Competitivity to J. Aguilera. We are also grateful for the CIBERNED funding awarded to Kulisevsky J. and the CONACyT-México scholarship (244867) awarded to V. Palafox-Sánchez.
Compliance with Ethical Standards
The experimental protocols were approved by the Ethics Committee of the Research Institute at the Hospital de la Santa Creu i Sant Pau and all procedures were conducted in compliance with Council Directive 2010/63EU of the European Parliament and the Council of 22 September 2010 on the protection of animals used for scientific purposes and the care and use of laboratory animals.
Conflict of Interest
The authors declare that they have no conflicts of interest.
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