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

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

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

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 FosB 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 FosB 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 FosB 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 1h post-injection, the levels returned to baseline values after 24h. After subchronic levodopa treatment, the levels of FosB and FosB mRNA expression were lower 1h 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 1h 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.

Original languageEnglish
Pages (from-to)563-574
Number of pages12
JournalNeurotoxicity Research
Volume35
Issue number3
DOIs
Publication statusPublished - 15 Apr 2019

Keywords

  • Animals
  • Antiparkinson Agents/pharmacology
  • Corpus Striatum/drug effects
  • Functional Laterality
  • Gene Expression/drug effects
  • Levodopa/pharmacology
  • Male
  • Parkinsonian Disorders/drug therapy
  • Proto-Oncogene Proteins c-fos/metabolism
  • RNA, Messenger/metabolism
  • Rats, Sprague-Dawley
  • Time Factors

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