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Deep sequencing of the small RNA transcriptome of blood leukocytes from Parkinson's disease patients prior to and following deep brain stimulation (DBS) and as compared with healthy control volunteers

ABSTRACT: We report the application of small RNA sequencing technology for high-throughput profiling of microRNA molecules (miRNAs) in blood leukocytes of Parkinson's Disease (PD) patients. Expression changes which may contribute to PD pathogenesis and reaction to treatment were identified in RNA preparations from blood leukocyte samples collected from PD patients prior to and following DBS neurosurgery on stimulation and following a short one hour cessation of the electrical stimulation (which enabled dissociation of the surgery effects from the electrical stimulation alone) and from matched healthy control volunteers, all under signed informed consents.

ORGANISM(S): Homo sapiens

PROVIDER: GSE40915 | GEO | 2013/11/21

SECONDARY ACCESSION(S): PRJNA176709

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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Deep sequencing of the small RNA transcriptome of blood leukocytes from Parkinson's disease patients prior to and following deep brain stimulation (DBS) and as compared with healthy control volunteers

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