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Gene expression profiling of parkinsonian substantia nigra

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE20333 | GEO | 2010/03/10

SECONDARY ACCESSION(S): PRJNA125401

REPOSITORIES: GEO

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Gene expression profiling of parkinsonian substantia nigra

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. Post-mortem human brains were obtained from moderately to severe parkinsonism individuals based on the Hoehn & Yahr criteria. All the subjects were negative for AD pathology according to Braak & Braak. The average age for PD and control is 76.6 and 77.8 years, respectively. The average postmortem delay for PD and control is 26.2 and 19.8 hours, respectively.

2010-03-23 | E-GEOD-20333 | biostudies-arrayexpress

Expression profiling of the Parkinsonian Brain

2008-01-01 | GSE8397 | GEO

Dysregulation of Gene Expression in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Lesioined Mouse Substantia Nigra

Project description:Parkinson's disease pathogenesis proceeds through several phases, culminating in the loss of dopaminergic neurons of the substantia nigra (SN). Although the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of oxidative SN injury is frequently used to study degeneration of dopaminergic neurons in mice and non-human primates, an understanding of the temporal sequence of molecular events from inhibition of mitochondrial complex 1 to neuronal cell death is limited. Here, microarray analysis and integrative data mining were used to uncover pathways implicated in the progression of changes in dopaminergic neurons after MPTP administration. This approach enabled the identification of small, yet consistently significant, changes in gene expression within the SN of MPTP-treated animals. Such an analysis disclosed dysregulation of genes in three main areas related to neuronal function: cytoskeletal stability and maintenance, synaptic integrity, and cell cycle and apoptosis. The discovery and validation of these alterations provide molecular evidence for an evolving cascade of injury, dysfunction, and cell death. Keywords: Parkinson's disease; MPTP; gene expression; microarray; cytoskeleton; mouse

2006-05-12 | GSE4788 | GEO

Transcription profiling of human Parkinsons medial and substania nigra

Project description:Affymetrix HG_U133 array sets (A and B chips) were used to determine the whole genome transcription profile of clinically documented and neuropathologically confirmed cases of sporadic Parkinson's disease as well as controls. Experiment Overall Design: Post mortem brain tissue samples from Parkinson's disease and control cases (substantia nigra, split into medial and lateral portions, and frontal cortex) were prepared for this study. In total, 47 individual tissue samples were analyzed using one A and one B GeneChip per sample, i.e. 15 samples of medial parkinsonian SN, 9 samples of lateral parkinsonian SN, 8 medial nigra control samples and 7 lateral nigra control samples. Lateral and medial nigra samples were from the same cases. In addition, frontal cerebral cortex was analyzed in five of the PD cases and in three of the controls (Neurogenetics 2006 7: 1â??11; Acta Neuropathologica (Berlin) 2007 113: 253-263

2008-06-16 | E-GEOD-8397 | biostudies-arrayexpress

Transcription profiling of dopaminergic neurons of the substantia nigra pars compacta (SNc) and the ventral tegmental area from normal rats

Project description:The cardinal clinical features of Parkinson's disease result from selective loss of midbrain dopaminergic neurons. The goal of this experiment is to determine the gene expression profiles of these neurons by studying untreated rat substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) dopaminergic neurons using laser capture microscopy to obtain region-specific neuronal mRNA.

2007-10-27 | E-GEOD-1157 | biostudies-arrayexpress

Gene expression profiling of substantia nigra: a post-mortem study in Parkinson's disease and control subjects

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.

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Age-mediated transcriptomic changes in adult mouse substantia nigra

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

Gene expression in Parkinson modeled mouse substantia nigra pars compacta at single cell resolution

Project description:Strong evidence in human populations indicates that pesticide exposure increases the risk of Parkinson's disease . However, to date there has no study investigating the role of genetic pathways for pesticide induced PD at cellular resolution. We used single cell RNA sequencing to provide fine-grained information on the genetic pathways of Parkinson's disease caused by a combined regimen of maneb and paraquat. We investigated the substantia nigra pars compacta of control mice and mice treated with maneb and paraquat to identify changes in gene expression in cellular subpopulations such as neurons, glia and vascular cells. This work reveals how neuronal and non-neuronal cells interact in the context of a toxicologically and environmentally relevant model Parkinson's disease, while offering entry points to the design of new therapies.

2021-11-03 | GSE187012 | GEO

Expression data of substantia nigra from postmortem human brain of Parkinson's disease patients (PD)

Project description:We used microarrays to detail the global program of gene expression underlying Parkinson's disease Keywords: normal versus diseased

2007-06-14 | GSE7621 | GEO

Ca2+ channels couple spiking to mitochondrial metabolism in substantia nigra dopaminergic neurons

Project description:How do neurons match generation of adenosine triphosphate (ATP) by mitochondria to the bioenergetic demands of regenerative activity? Although the subject of speculation, this coupling is still poorly understood, particularly in neurons that are tonically active. To help fill this gap, pacemaking substantia nigra dopaminergic neurons were studied using a combination of optical, electrophysiological and molecular approaches. In these neurons, spike-activated calcium (Ca2+) entry through Cav1 channels triggered Ca2+ release from the endoplasmic reticulum, which stimulated mitochondrial OXPHOS through two complementary Ca2+-dependent mechanisms: one mediated by the mitochondrial uniporter and another by the malate-aspartate shuttle. Disrupting either mechanism impaired the ability of dopaminergic neurons to sustain spike activity. While this feedforward control helps dopaminergic neurons meet the bioenergetic demands associated with sustained spiking, it also is responsible for their elevated oxidant stress and possibly to their decline with aging and disease.

2022-07-31 | GSE206366 | GEO

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