Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human Parkinsons medial and substania nigra

ABSTRACT: 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

ORGANISM(S): Homo sapiens

SUBMITTER: Linda Moran

PROVIDER: E-GEOD-8397 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Whole genome expression profiling of the medial and lateral substantia nigra in Parkinson's disease.

Moran L B LB Duke D C DC Deprez M M Dexter D T DT Pearce R K B RK Graeber M B MB

Neurogenetics 20060112 1

We have used brain tissue from clinically well-documented and neuropathologically confirmed cases of sporadic Parkinson's disease to establish the transcriptomic expression profile of the medial and lateral substantia nigra. In addition, the superior frontal cortex was analyzed in a subset of the same cases. DNA oligonucleotide microarrays were employed, which provide whole human genome coverage. A total of 570 genes were found to be differentially regulated at a high level of significance. A la ...[more]

PMID: 16344956

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Project description:Implications for neuroprotection in Parkinson's disease Parkinson’s disease and its characteristic symptoms are thought to arise from the progressive degeneration of specific midbrain dopamine (DA) neurons. In humans, DA neurons of the substantia nigra (SN) and their projections to the striatum show selective vulnerability, while neighboring DA neurons of the ventral tegmental area (VTA) are relatively spared from degeneration. This pattern of cell loss is mimicked in humans, primates, and certain rodents by the neurotoxin MPTP. In this study, we aimed to test the hypothesis that there are factors in the VTA that are potentially neuroprotective against MPTP and that these factors change over time. We have found a differential transcriptional response within the cells of the SN and VTA to sustained exposure to a low dose of MPTP. Specifically, the VTA has increased expression of 148 genes as an early response to MPTP and 113 genes as a late response to MPTP toxicity. This response encompasses many areas of cellular function, including protein regulation (Phf6) and ion/metal regulation (PANK2, Car4). Notably, these responses were largely absent from the cells of the SN. Our data show a clear dynamic response in maintaining the homeostasis and viability of the neurons in the VTA that is lacking in the SN after neurotoxin challenge. We used microarrays to analyze the differential response of the substantia nigra (SN) and ventral tegmental area (VTA) to a chronic low dose of the neurotoxin MPTP. Transgenic hTH-GFP mice were treated with MPTP (4mg/kg) for either 2 or 10 days. Control mice were given an equal volume of saline for 10 days. Dopamine neurons from the substantia nigra and ventral tegmental areas of control and MPTP treated animals were laser captured. The RNA was isolated and processed for microarray hybridization. Each group had three biological replicates, for a total of 18 samples. Three each in the following: Control SN, Control VTA, 2 day MPTP SN, 2 day MPTP VTA, 10 day MPTP SN, 10 day MPTP VTA. Samples were log2 transformed and RMA normalized using Agilent Genespring 10.0 GX.

Dataset Information

Transcription profiling of human Parkinsons medial and substania nigra

Publications

Whole genome expression profiling of the medial and lateral substantia nigra in Parkinson's disease.

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