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Whole-transcriptome high-throughput RNA sequencing of blood leukocytes from Parkinson's disease human patients pre- and post-deep brain stimulation

ABSTRACT: The given data set is the first deep sequencing transcriptome-wide data set of human Parkinson's disease (PD) patients RNA. The data set was produced from blood leukocytes of PD patients, from the same patients following deep brain stimulation (DBS), and from matched healthy control volunteers. Post-DBS samples were taken from the patients while being on electrical stimulation (ON-Stim), and following one hour off of electrical stimulation (OFF-Stim state). We have previously shown that gene expression changes, and in particular, alternative splicing changes, are observed in blood leukocytes and may contribute to PD and being subjected to regulation following DBS. Here, SOLiD RNA-Seq was applied to study the transcriptome of PD patients. Exon- and junction-level analyses revealed deep insight into both differential expression and alternative splicing regulation in PD blood leukocytes prior to and following DBS both on and off electrical stimulation. This transcriptome genome-wide data obtained through high-throughput sequencing of RNA produced from human Parkinson's disease (PD) patients blood leukocytes prior to treatment and following deep brain stimulation (DBS) neurosurgical treatment may yield insights into the molecular mechanisms that underlie the pathogenesis of PD and treatment efficacy. It may further enable the development of future diagnostics and therapeutics for PD.

ORGANISM(S): Homo sapiens

PROVIDER: GSE42608 | GEO | 2014/07/16

SECONDARY ACCESSION(S): PRJNA209490

REPOSITORIES: GEO

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Project description:Sub-thalamic deep brain stimulation (DBS) reversibly modulates ParkinsonM-bM-^@M-^Ys disease (PD) motor symptoms, providing an unusual opportunity to compare leukocyte transcripts in the same subjects before and after neurosurgery and after disconnecting the stimulus (ON-and OFF-stimulus). Here, we report rapid stimulus-induced and largely reversible changes in PD leukocyte transcripts, which were larger in scope than the disease-induced changes. These transcript changes classified advanced pre- from post-surgery PD patients and discriminated patients from controls. Moreover, the extent of changes correlated with the neurological efficacy of the DBS neurosurgery, and covered both regulatory pathways and individual transcript changes, e.g. SNCA, PARK7 and the splicing factor SFRS1. Following 1 hour OFF-stimulus, these changes were largely reversed. We extracted from these differences a modified transcripts signature which discriminated controls from advanced PD patients, pre- from post-surgery and ON-from OFF-stimulus conditions. A further gene-list independent analysis detected reversed pathways. Our findings suggest future uses of this approach and the discovered molecular signature for early diagnostics of PD and for identifying novel targets for therapeutic intervention in this and other DBS-treatable neurological diseases. 27 Total samples were analyzed. Study design included four conditions. PD patients (n=7) leukocyte blood samples were examined at 3 time points, and healthy control subjects (n=6) were examined once each. Samples were taken 1 day prior to sub-thalamic nucleous (STN) DBS treatment, several months after STN-DBS treatment upon optimal stimulation and following one hour electrical stimulation cessation. The off stimulation caused recruitment of the disease symptoms as measured by the Unified Parkinson's Disease Rating Scale motor section (UPDRS-III). The different stages are designated: S1 (pre-treatment), S2 (post STN-DBS) and S3 (upon off stimulation). All patients were on dopamine replacement therapy (DRT) when examined pre- and post-DBS off stimulation (albeit with reduced therapy dose post-DBS). To reduce biological variability among the samples which is not related to the study, only male subjects were included in this study. Samples from six age- and gender- matched healthy control subjects served to detect disease modified transcripts and for pre- and post- treatment comparisons. The study was approved by the human review board at the Hadassah University Hospital, Ein-Kerem (no. 6-07.09.07) in accordance with the Declaration of Helsinki. All study participants signed informed consent.

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Whole-transcriptome high-throughput RNA sequencing of blood leukocytes from Parkinson's disease human patients pre- and post-deep brain stimulation

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