Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Human Splice Junction Arrays of Parkinson's Patients Leukocytes mRNA Pre- and Post-Deep Brain Stimulation

ABSTRACT: Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide and the first involving motor symptoms. Deep brain stimulation (DBS) neurosurgery treatment through electrodes implanted to the subthalamic nucleus (STN) improves dramatically the debilitating motor symptoms of the disease due to yet unknown molecular mechanisms. Affymetrix human junction prototype microarrays (HJAY) of blood leukocytes mRNA from PD patients prior to, and following DBS neurosurgery treatment on electrical stimulation were compared to these of age- and gender-matched healthy control volunteers. About 95% of all human genes undergo alternative splicing, and alternative splicing is involved in human diseases and specifically in neurodegenerative diseases. Thus, the goal of this study was to detect alternatively spliced genes in PD patients prior to, and following DBS and to predict the effect of these on the functional level of change at the transcript level (such as exon inclusion, intron retention and nonsense-mediated decay events). Understanding the role of alternative splicing in neurodegenerative diseases will open new avenues to future novel approaches for early detection and neuroprotective treatment enabled by the development of future genetic therapeutics targeted at specific modified splice variants. A total of 11 blood leukocytes mRNA samples were analyzed: four from Parkinson's Disease (PD) patients pre-DBS treatment, three from PD patients tested again post-DBS (while being on electrical stimulation), three from age- and gender-matching healthy control (HC) volunteers, and one PD sample pre-DBS sample was re-stained and rescanned .

ORGANISM(S): Homo sapiens

SUBMITTER: Lilach Soreq

PROVIDER: E-GEOD-37591 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Small RNA sequencing-microarray analyses in Parkinson leukocytes reveal deep brain stimulation-induced splicing changes that classify brain region transcriptomes.

Soreq Lilach L Salomonis Nathan N Bronstein Michal M Greenberg David S DS Israel Zvi Z Bergman Hagai H Soreq Hermona H

Frontiers in molecular neuroscience 20130513

MicroRNAs (miRNAs) are key post transcriptional regulators of their multiple target genes. However, the detailed profile of miRNA expression in Parkinson's disease, the second most common neurodegenerative disease worldwide and the first motor disorder has not been charted yet. Here, we report comprehensive miRNA profiling by next-generation small-RNA sequencing, combined with targets inspection by splice-junction and exon arrays interrogating leukocyte RNA in Parkinson's disease patients before ...[more]

PMID: 23717260

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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.

Dataset Information

Human Splice Junction Arrays of Parkinson's Patients Leukocytes mRNA Pre- and Post-Deep Brain Stimulation

Publications

Small RNA sequencing-microarray analyses in Parkinson leukocytes reveal deep brain stimulation-induced splicing changes that classify brain region transcriptomes.

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