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Series GSE176004 Query DataSets for GSE176004
Status Public on Jun 03, 2021
Title Riluzole administration to rats with levodopa-induced dyskinesia analyzed by RRBS
Organism Rattus norvegicus
Experiment type Methylation profiling by high throughput sequencing
Summary 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 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 more than 20% methylation difference relative to levodopa treatment alone. These findings indicate potential new druggable targets for levodopa-induced dyskinesia.
Overall design 3 groups of 3 rats after unilateral 6-OHDA lesion and no treatment or L-DOPA treatment or L-DOPA + Riluzole treatment for 2 weeks. Analysis of both striata from each animal.
Contributor(s) Pagliaroli L, Fothi A, Aranyi T
Citation(s) 34207710
Submission date Jun 02, 2021
Last update date Aug 03, 2022
Contact name Ábel Fóthi
Organization name Institute of Enzymology, RCNS
Street address Magyar Tudosok korutja 2.
City Budapest
State/province Please Select
ZIP/Postal code 1117
Country Hungary
Platforms (1)
GPL14844 Illumina HiSeq 2000 (Rattus norvegicus)
Samples (18)
GSM5352558 Untreated control side_rep 1
GSM5352559 Untreated control side_rep 2
GSM5352560 Untreated control side_rep 3
BioProject PRJNA734572
SRA SRP322345

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Supplementary file Size Download File type/resource
GSE176004_RAW.tar 329.9 Mb (http)(custom) TAR (of TXT)
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Raw data are available in SRA
Processed data provided as supplementary file

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