Unknown,Transcriptomics,Genomics,Proteomics

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Gene expression differences between striatum of vehicle- or L-DOPA-treated FRL and FSL rats

ABSTRACT: Total RNA was extracted from the striatum of vehicle- or L-DOPA-treated FRL and FSL rats. After quality control, RNA samples were submitted to the Gene Expression Service Workflow of Roche NimbleGen, which included hybridization with a Roche NimbleGen Rat Gene Expression 12x135K Array (Design Name 100718_Rat_HX12_expr), array scanning, data extraction and processing. Normalized gene expression data (\\"Normalized Calls\\") provided by Roche NimbleGen were analyzed using ANAIS [Simon and Biot, Bioinformatics 2010 Oct; 26(19):2468-9] via the \\"Norm genes\\" function. Genes were considered differentially expressed if their transcript abundance (scanned signal intensity) was ≥1.5-fold higher or lower in at least one experimental group compared to striatum of vehicle-treated FRL rats. The resulting list of 6040 genes was imported into Microsoft Excel, where only those genes with ANAIS-computed ANOVA p-values <0.05 were retained.

ORGANISM(S): Rattus rattus

SUBMITTER: per svenningsson

PROVIDER: E-MTAB-8822 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:This study addresses the molecular mechanisms underlying the action of subthalamic nucleus high frequency stimulation (STN-HFS) in the treatment of ParkinsonM-bM-^@M-^Ys disease and its interaction with levoDOPA (L-DOPA), focusing on the striatum. The objectives were 1) to identify the molecular signature of STN-HFS action at striatal level, associated with its efficient antiparkinsonian action, and 2) to investigate the molecular substrates of the interaction between the two treatments in order to evidence possible genes involved in dyskinesia. Striatal gene expression profile was assessed in rats with nigral DOPAmine neuron lesion, either treated or not, using agilent microarrays and qPCR verification. The treatments consisted in anti-akinetic STN-HFS (5 days), chronic L-DOPA treatment inducing dyskinesia (LIDs) or the combination of the two treatments that exacerbated LIDs. STN-HFS modulated 71 genes with functional or biochemical annotation, including genes sharing the GO terms regulation of growth, regulation of apoptosis, extracellular region. Ttr, Igf2, Sostdc1 and Nr4A3 (Nor-1), are among the 5 genes showing the highest specific upregulation. Down-regulated genes include Prkcd, Sirt5 and Bbc3. These results show that genes involved in neuroprotection and/or neurogenesis are key components of STN-HFS action in the striatum. STN-HFS and LDOPA treatment share very few common gene regulation features suggesting that the molecular substrates underlying their striatal action are mostly different. In addition to genes already reported to be associated with LIDs (Pdyn, Trh, Grm4/mGlu4, Cnr1/CB1), the comparison between DOPA and DOPA/STN-HFS identifies immunity-related genes: C1s, Rt1-Da and Irf7a, as potential players in L-DOPA side effects. Total RNA was extracted from striatal tissue from four groups of 3 animals bearing 6-hydroxyDOPAmine (6-OHDA)-induced lesion of the nigrostriatal DA pathway: lesion alone without any subsequent treatment (L), L-DOPA treatment for 19 days (D), STN-HFS for 5 days (S) and combination of L-DOPA and STN-HFS (DS).

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Gene expression differences between striatum of vehicle- or L-DOPA-treated FRL and FSL rats

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