Riluzole administration to rats with levodopa-induced dyskinesia leads to loss of DNA methylation in neuronal genes
| Autor: | Flora Szeri, Luca Pagliaroli, Csaba Barta, Bastian Hengerer, Ábel Fóthi, István Likó, Borbala Veto, Piroska Dévay, Ester Nespoli, Tamas Aranyi |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Epigenomics
Levodopa Dyskinesia Drug-Induced abnormal involuntary movements QH301-705.5 Pharmacology Article Tourette-Syndrom mental disorders medicine otorhinolaryngologic diseases Animals Epigenetics ddc:610 Biology (General) Rats Wistar Medial forebrain bundle Epigenetik Levodopa-induced dyskinesia Dyskinesias DNA methylation Riluzole epigenetics business.industry Tourette syndrome L-Dopa Dyskinesie Riluzol General Medicine Reduced Representation Bisulfite Sequencing (RRBS) Abnormal involuntary movement Corpus Striatum Rats nervous system diseases dyskinesia Dyskinesia medicine.symptom business DDC 610 / Medicine & health medicine.drug |
| Zdroj: | Cells Volume 10 Issue 6 Cells, Vol 10, Iss 1442, p 1442 (2021) |
| DOI: | 10.18725/oparu-45713 |
| Popis: | Dyskinesias are characterized by abnormal repetitive involuntary movements due to dysfunctional neuronal activity. Although levodopa-induced dyskinesia, characterized by tic-like abnormal involuntary movements, has no clinical treatment for Parkinson’s disease patients, animal studies indicate that Riluzole, which interferes with glutamatergic neurotransmission, can improve the phenotype. The rat model of Levodopa-Induced Dyskinesia is a unilateral lesion with 6-hydroxydopamine in the medial forebrain bundle, followed by the repeated administration of levodopa. The molecular pathomechanism of Levodopa-Induced Dyskinesia is still not deciphered; however, the implication of epigenetic mechanisms was suggested. In this study, we investigated the striatum for DNA methylation alterations under chronic levodopa treatment with or without co-treatment with Riluzole. Our data show that the lesioned and contralateral striata have nearly identical DNA methylation profiles. Chronic levodopa and levodopa + Riluzole treatments led to DNA methylation loss, particularly outside of promoters, in gene bodies and CpG poor regions. We observed that several genes involved in the Levodopa-Induced Dyskinesia underwent methylation changes. Furthermore, the Riluzole co-treatment, which improved the phenotype, pinpointed specific methylation targets, with a more than 20% methylation difference relative to levodopa treatment alone. These findings indicate potential new druggable targets for Levodopa-Induced Dyskinesia. publishedVersion |
| Databáze: | OpenAIRE |
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