Project description:Transcriptional analysis of multiple brain regions in Parkinson's disease supports the involvement of specific protein processing, energy metabolism, and signaling pathways, and suggests novel disease mechanisms. This SuperSeries is composed of the following subset Series: GSE20168: Transcriptional analysis of prefrontal area 9 in Parkinson's disease GSE20291: Transcriptional analysis of putamen in Parkinson's disease GSE20292: Transcriptional analysis of whole substantia nigra in Parkinson's disease Refer to individual Series
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. Examination of substantia nigra from postmortem brains of 8 patients with Parkinson's disease (PD).
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:In this study we identify the gene expression changes that occur in the brain-localized immune cells in a mouse model of Parkinson's Disease. A mouse model of Parkinson's Disease 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 mice, while control mice were injected with empty vector (EV). These mice exhibit neurodegeneration in the Substantia Nigra and Parkinson-like behaviour phenotypes. Sixteen weeks after the injection, the Substantia Nigra and Srtiatum were micro-dissected and a Percoll gradient was used to enrich for the immune cells present in these tissues. The immune cells were also isolated from the Substantia Nigra and Striatum of same-age WT uninjected mice (WT). RNA was isolated from these cells and single-end 75nt high throughput sequencing were performed on libraries prepared from the RNA. We identified over 400 genes that were differentially expressed between control and Parkinson's mice with a log2 fold-change > |0.75|. These genes were enriched for terms related to immune activation such as: cytokine processing, leukocyte activation, and antigen presentation. The genes associated with these GO terms tended to be up-regulated in the Parkinson's mice suggesting that brain-localized immune cells are more activated in Parkinson's disease.
Project description:In order to investigate the effect of Alpha-Ketoglutarate (AKG) on p-α-synuclein in substantia nigra of Parkinson's disease (PD) model mice (C57BL/6), we profiled substantia nigra from wild-type (WT), AAV-α-synuclein (α-Syn), AKG and α-Syn-AKG in male mice by RNA sequencing (RNA-seq).
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: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.
Project description:Detailed analysis of disease-affected tissue provides insight into molecular mechanisms contributing to pathogenesis. Substantia nigra, striatum and cortex are functionally connected with increasing degrees of alpha-synuclein pathology in Parkinson's disease. Functional and causal pathway analysis of gene expression and proteomic alterations in these three regions revealed pathways that correlated with deposition of alpha-synuclein. Microarray and RNAseq experiments revealed previously unidentified causal changes related to oligodendrocyte function and synaptic vesicle release and other changes were reflected across all brain regions. Importantly a subset of these changes were replicated in Parkinson's disease blood. Proteomic assessment revealed alterations in mitochondria and vesicular transport proteins that preceded gene gene expression changes indicating defects in translation and/or protein turnover. Our combined approach of proteomics, RNAseq and microarray analyses provides a comprehensive view of the molecular changes that accompany alpha-synculein pathology in Parkinson's disease, and may be instrumental in understanding and diagnosing Parkinson's disease progression. Substantia Nigra (3 normal, 3 PD), Striatum (6 normal, 6 PD), Cortex (5 normal, 5 PD), Cortex non-PD neurodegeneration (2 normal, 3 DLB). Note Sample X201264 was used both for Cortex normal and for Cortex nonPD normal