Expression data of substantia nigra from postmortem human brain of Parkinson's disease patients (PD)
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE7621 | GEO | 2007/06/14
SECONDARY ACCESSION(S): PRJNA100241
REPOSITORIES: GEO
Similar Datasets
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.
2008-11-06 | E-GEOD-7621 | biostudies-arrayexpress
Project description:Introduction: Parkinson's disease (PD) is characterized by bradykinesia, tremor, and rigidity; in addition, postural instability sets in as the disease progresses. Non-motor symptoms of the disease include cognitive, behavioral, and neuropsychiatric changes, sensory and sleep disturbances that may precede the motor symptoms of the disease itself. The peculiar pathological features of PD are decreased dopaminergic neurons and dopamine levels in the substantia nigra pars compacta and pontine locus ceruleus. The study of the transcriptome plays a major role in the identification of genes and gene regulatory mechanisms in multifactorial neurodegenerative diseases such as Parkinson's disease itself. Therefore, we proposed to study the transcriptome directly in the midbrain containing the "Substantia nigra.The study was performed in 8 subjects with PD and 6 normal control subjects, using next-generation sequencing (NGS) technologies. Results: With the use of an ad hoc bioinformatics pipeline, gene expression profiles in the different PD subjects were obtained and compared to those of controls. In detail, the results obtained from the data analysis indicated 92 differentially expressed genes (FDR-adjusted p value ≤0.05 and fold-change less than -1.5 or greater than +1.5) of which 33 genes were up-regulated while 59 were down-regulated. Conclusions: Functional analysis of the differentially expressed genes revealed several genes involved in different canonical pathways indicating their likely significant role in Parkinson's disease.
2024-01-03 | E-MTAB-13295 | biostudies-arrayexpress
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.
2024-12-09 | GSE263579 | GEO
Project description:Affymetrix HG-Focus array was used to determine a global gene expression profile of clinically and neuropathologically confirmed cases of sporadic Parkinson's disease compared to controls. Major alterations were detected in signal transduction, protein degradation, dopaminergic transmission/metabolism, energy pathways/glycolysis, cell adhesion/cytoskeleton, extracellular matrix components and cell cycle functional classes.
2010-03-10 | GSE20333 | GEO
Project description:Single-Cell Transcriptomics of Human Substantia Nigra in Parkinson's Disease
| PRJNA767088 | ENA
Project description:The substantia nigra (SN) provides the largest dopaminergic input to the brain, projects to the striatum (the primary locus of action for antipsychotic medication), and receives GABAergic and glutamatergic inputs. This study used western blot analysis to compare protein levels of tyrosine hydroxylase (TH), glutamate decarboxylase (GAD67), and vesicular glutamate transporters (vGLUT1 and vGLUT2) in postmortem human SN in schizophrenia subjects (n=13) and matched controls (n=12). As a preliminary analysis, the schizophrenia group was subdivided by (1) treatment status: off medication (n=4) or on medication (n=9); or (2) treatment response: treatment resistant (n=5) or treatment responsive (n=4). The combined schizophrenia group had higher TH and GAD67 protein levels than controls (an increase of 69.6%, P=0.01 and 19.5%, P=0.004, respectively). When subdivided by medication status, these increases were found in the on-medication subjects (TH 88.3%, P=0.008; GAD67 40.6%, P=0.003). In contrast, unmedicated schizophrenia subjects had higher vGLUT2 levels than controls (an increase of 28.7%, P=0.041), but vGLUT2 levels were similar between medicated schizophrenia subjects and controls. Treatment-resistant subjects had significantly higher TH and GAD67 levels than controls (an increase of 121.0%, P=0.0003 and 58.7%, P=0.004, respectively). These data suggest increases in dopamine and GABA transmission in the SN in schizophrenia, with a potential relation to treatment and response.
| S-EPMC5399235 | biostudies-literature
Project description:Substantia nigra pars compacta (SNpc) is highly sensitive to normal aging and selectively degenerates in Parkinson's disease. Until now, molecular mechanisms behind SNpc aging have not been fully investigated using high throughput techniques. Here, aging-associated early changes in transcriptome of SNpc were investigated comparing late middle-aged (18 months old) to young (2 months old) mice.
2013-05-29 | GSE45043 | GEO
Project description:Post mortem tissue was dissected from two groups of age and gender matched groups of Parkinson and Control subjects
2010-03-12 | GSE20292 | GEO
Project description:BackgroundParkinson's disease (PD) is the most common neurodegenerative disorder involving the motor system. Although not being the only region involved in PD, affection of the substantia nigra and its projections is responsible for some of the most debilitating features of the disease. To further advance a comprehensive understanding of nigral pathology, we conducted a tissue based comparative proteome study of healthy and diseased human substantia nigra.ResultsThe gross number of differentially regulated proteins in PD was 221. In total, we identified 37 proteins, of which 16 were differentially expressed. Identified differential proteins comprised elements of iron metabolism (H-ferritin) and glutathione-related redox metabolism (GST M3, GST P1, GST O1), including novel redox proteins (SH3BGRL). Additionally, many glial or related proteins were found to be differentially regulated in PD (GFAP, GMFB, galectin-1, sorcin), as well as proteins belonging to metabolic pathways sparsely described in PD, such as adenosyl homocysteinase (methylation), aldehyde dehydrogenase 1 and cellular retinol-binding protein 1 (aldehyde metabolism). Further differentially regulated proteins included annexin V, beta-tubulin cofactor A, coactosin-like protein and V-type ATPase subunit 1. Proteins that were similarly expressed in healthy or diseased substantia nigra comprised housekeeping proteins such as COX5A, Rho GDI alpha, actin gamma 1, creatin-kinase B, lactate dehydrogenase B, disulfide isomerase ER-60, Rab GDI beta, methyl glyoxalase 1 (AGE metabolism) and glutamine synthetase. Interestingly, also DJ-1 and UCH-L1 were expressed similarly. Furthermore, proteins believed to serve as internal standards were found to be expressed in a constant manner, such as 14-3-3 epsilon and hCRMP-2, thus lending further validity to our results.ConclusionUsing an approach encompassing high sensitivity and high resolution, we show that alterations of SN in PD include many more proteins than previously thought. The results point towards a heterogeneous aetiopathogenesis of the disease, including alterations of GSH-related proteins as well as alterations of proteins involved in retinoid metabolism, and they indicate that proteins involved in familial PD may not be differentially regulated in idiopathic Parkinson's disease.
| S-EPMC2265686 | biostudies-literature
Project description:Parkinson's disease (PD) is the second most common neurodegenerative disorder, and aging and genetic and environmental exposure can contribute to its pathogenesis. DNA methylation has been suggested to play a pivotal role in neurodevelopment and neurodegenerative diseases. 5-hydroxymethylcytosine (5hmC) is generated through 5-methylcytosine (5mC) oxidization by ten-eleven translocation proteins and is particularly enriched in the brain. Although 5hmC has been linked to multiple neurological disorders, little is known about 5hmC alterations in the substantia nigra of patients with PD. To determine the specific alterations in DNA methylation and hydroxymethylation in PD brain samples, we examined the genome-wide profiles of 5mC and 5hmC in the substantia nigra of patients with PD and Alzheimer's disease (ad). We identified 4119 differentially hydroxymethylated regions (DhMRs) and no differentially methylated regions (DMRs) in the postmortem brains of patients with PD compared with those of controls. These DhMRs were PD-specific when compared with the results of AD. Gene ontology analysis revealed that several signaling pathways, such as neurogenesis and neuronal differentiation, were significantly enriched in PD DhMRs. KEGG enrichment analysis revealed substantial alterations in multiple signaling pathways, including phospholipase D (PLD), cAMP and Rap1. In addition, using a PD Drosophila model, we found that one of the 5hmC-modulated genes, PLD1, modulated α-synuclein toxicity. Our analysis suggested that 5hmC may act as an independent epigenetic marker and contribute to the pathogenesis of PD.
| S-EPMC9558850 | biostudies-literature