Project description:Systematic meta-analysis and replication of genome-wide expression studies identifies molecular pathways of Parkinson's disease. Analysis of substantia nigrae from postmortem brains of 6 patients with Parkinson's disease (PD). Results provide insight into the molecular processes perturbed in the PD substantia nigra.
Project description:Systematic meta-analysis and replication of genome-wide expression studies identifies molecular pathways of Parkinson's disease. Analysis of substantia nigrae from postmortem brains of 6 patients with Parkinson's disease (PD). Results provide insight into the molecular processes perturbed in the PD substantia nigra. Substantia nigra samples from 6 PD and 5 control subjects were obtained. At autopsy, brain hemispheres were frozen in liquid nitrogen and stored at -80C in the Kathleen Price Bryan Brain Bank in the Alzheimer's Disease Research Center at Duke University. Using the RNAgents kit (Promega, Madison, Wis), RNA was extracted from SN and adjacent midbrain tissues. Double-stranded complementary DNA was made with a biotinylated T7(dT)-24 primer. Twenty micrograms of biotinylated complementary RNA was fragmented and hybridized to Affymetrix human genome U133A microarrays. The Affymetrix .CEL files were normalized to "all probe sets" in a standardized matter, and scaled to 100 by the MAS5 algorithm implemented in the Bioconductor package.
Project description:Systematic meta-analysis and replication of genome-wide expression studies identifies molecular pathways of Parkinson's disease. Examination of substantia nigra from postmortem brains of 8 patients with Parkinson's disease (PD).
Project description:Systematic meta-analysis and replication of genome-wide expression studies identifies molecular pathways of Parkinson's disease. Examination of substantia nigra from postmortem brains of 8 patients with Parkinson's disease (PD). The substantia nigra samples from 8 PD subjects were obtained from the Human Brain and Spinal Fluid Resource Center, VAMC, Los Angeles, CA, the Mind Unit Brain Bank at the University of Rochester, Rochester, NY, and from Dr. E. Masliah at UCSD, San Diego, CA, and 9 control subjects were obtained from the University of Rochester Alzheimer's Disease Center brain bank. The RNA was extracted using Trizol reagent (Invitrogen), DNAse treated with Qiagen DNAse, and analyzed on a bioanalyzer. The complementary RNA was fragmented and hybridized to Affymetrix human U133A arrays. The total 17 Affymetrix .CEL files were normalized to "all probe sets" in a standardized matter, and scaled to 100 by the MAS5 algorithm implemented in the Bioconductor package.
Project description:We used microarrays to detail the global program of gene expression underlying Parkinson's disease Experiment Overall Design: Substantia nigra tissue from postmortem brain of normal and Parkinson disease patients were used for RNA extraction and hybridization on Affymetrix microarrays: 9 replicates for the controls and 16 replicates for the Parkinson's disease patients were used. Both cohorts included males and females.
Project description:Analysis of substantia nigra from postmortem brains of 4 patients with Parkinson’s disease (PD). Results provide insight into the molecular processes perturbed in the PD substantia nigra.
Project description:Parkinson's disease (PD) is the second most common neurodegenerative disease, involving the selecive death of dopaminergic neurons in the substantia nigra pars compacta brain region. Here, we performed next generation sequencing on RNA extracted from human substantia nigra tissue. The samples, acquired from the Netherland's Brain Bank, were taken post-mortem from PD and non-PD control donors. Analysis of the data revealed an upregulation of lncRNA LINC-PINT in PD substantia nigra. LINC-PINT interracts with the Polycomb Repressive Complex 2 (PRC2), inhibiting the tracription of multiple targets. Correspondingly, analysis of the data revealed that targets of PRC2 displayed larger disease-associated differences as compared to other genes, as well as enrichment for downregulation, suggesting that the differential expression of LINC-PINT in PD effects LINC-PINT/PRC2 interaction as well.
Project description:Analysis of human dopamine (DA) from postmortem brains of 8 patients with Parkinson’s disease (PD). Results provide insight into the molecular processes perturbed in the PD substantia nigra.
Project description:In this study we identify the gene espression changes that occur in the substantia nigra in a Parkinson's Disease (PD) rat model with and without deep brain stimulation (DBS). A rat model of PD was created as previously described by stereotacticaly injecting an AAV-expressing the human A53T_mutated form of a-Synuclein into the Substantia Nigra of adult rats, while control rats were injected with empty vector (EV). These mice exhibit neurodegeneration in the Substantia Nigra and Parkinson-like behaviour phenotypes. Sixteen weeks after the injection, RNA was isolated from the Substantia Nigra and Striatum. Single-end 75nt high throughput sequencing were performed on libraries prepared from the RNA. We identified over 200 genes that were differentially expressed between control and Parkinson's ratswith a log2 fold-change > |0.6|. These genes were enriched for terms related to immune activation. The genes associated with these GO terms tended to be up-regulated in the Parkinson's rats suggesting that brain-localized immune cells are more activated in Parkinson's disease. Interestingly in the rats treated with DBS, these immune-related genes were comparable to control animals.
Project description:We characterize differentially spliced genes in postmortem human substantia nigra samples derived from various disease conditions, and discover a novel Parkinson's disease-associated splice variant, DJ-1 lacking exon 6.