Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcriptional interaction network analyses in dorsal nucleus of vagus nerve, locus coeruleus and substantia nigra in Parkinson's disease

ABSTRACT: We analyzed the transcriptomic profile of post-mortem explants from dorsal nucleus of vagus nerve, locus coeruleus and substantia nigra obtained from controls and Braak 4 (BK4) and 5 (BK5) stages of Parkinson’s disease (PD) patients in order to investigate how gene-gene interaction patterns vary along different anatomical regions in patients and controls. The comparative transcriptional networks analyses indicate that the main hubs in PD networks are related to ubquitin/proteasome, oxidative stress, neuroprotection, neurogenesis and PD associated proteins. Transcriptomic profiles of controls and Parkinson’s disease patients were compared using SAM test for LC or Wilcoxon Mann-Whitney test for SN and VA (p<0.005 and p<0.01, respectively) in order to identify differentially expressed transcripts.

ORGANISM(S): Homo sapiens

SUBMITTER: Carlos Moreira-Filho

PROVIDER: E-GEOD-43490 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Publications

Complex network-driven view of genomic mechanisms underlying Parkinson's disease: analyses in dorsal motor vagal nucleus, locus coeruleus, and substantia nigra.

Corradini Beatriz Raposo BR Iamashita Priscila P Tampellini Edilaine E Farfel José Marcelo JM Grinberg Lea Tenenholz LT Moreira-Filho Carlos Alberto CA

BioMed research international 20141126

Parkinson's disease (PD)—classically characterized by severe loss of dopaminergic neurons in the substantia nigra pars compacta—has a caudal-rostral progression, beginning in the dorsal motor vagal nucleus and, in a less extent, in the olfactory system, progressing to the midbrain and eventually to the basal forebrain and the neocortex. About 90% of the cases are idiopathic. To study the molecular mechanisms involved in idiopathic PD we conducted a comparative study of transcriptional interactio ...[more]

PMID: 25525598

Similar Datasets

Project description:Down syndrome (DS) patients frequently develop organ-specific autoimmune disorders, particularly endocrinopathies and coeliac disease, as well as an increased susceptibility to mucosal candidiasis. These clinical features resemble APECED (autoimmune-polyendocrinopathy-candidiasis-ectodermal-dystrophy), a monogenic condition due to mutations in the AIRE gene, located on 21q22.3 and already described as down-regulated in 21 trisomy. Here we investigated AIRE expression and global gene expression profiles in surgically removed thymuses from 14 DS infants and children with congenital heart defects and from 42 age-matched individuals with cardiac defect as an isolated malformation. Immunohistochemistry revealed significantly reduced AIRE expression in DS thymuses (70.48M-BM-149.59 positive cells/mm2 in DS X 154.70M-BM-161.16 in controls, p<0.0001). qPCR confirmed the lower expression of AIRE in DS thymuses. Global thymic RNA profiles from DS patients and controls revealed 407 genes significantly hypoexpressed in DS. Network transcriptional analysis showed that hypoexpressed genes are related to biological processes such as antigen processing and presentation of endogenous antigen (ERAP2, CD1D), negative (PRDX2) and positive (CD3D, CD74) thymic T-cell selection and homeostasis of number of cells (PRDX2). Altogether these findings may explain the high prevalence of autoimmune phenomena in DS patients. Moreover, our data are in accordance with previous findings of thymic abnormal development in DS patients, characterized by lymphocyte depletion, diminution of the cortex, and loss of corticomedullary demarcation. Global gene profiles indicate that in DS patients, the trisomic imbalance probably leads to thymic hypofunction. In conclusion, lower AIRE expression and the impairment of other crucial pathways for central tolerance could well explain the high prevalence of organ-specific autoimmune disorders in DS. Among the 14 DS infants and 42 age-matched individuals with cardiac defect, only 4 from each group provided enough biological material (thymus fragments) for isolation of high-quality RNA to perform array analysis. Eight thymic samples were analyzed: C1, C2, C3 and C4 are controls, and D1, D2, D3 and D4 are from patients with Down syndrome.

Project description:Samples used in the study originated from three UK sites: the Walton Centre for Neurology and Neurosurgery in Liverpool, the Salford Royal Hospital in Salford and the Southern General Hospital in Glasgow. We recruited patients with pharmacoresistant mesial temporal lobe epilepsy for whom a therapeutic temporal lobectomy was being undertaken. After surgery, the hippocampus was divided into two portions: (1) one portion was preserved for RNA isolation, and (2) the other portion underwent histological analysis by an experienced neuropathologist. Frozen post-mortem histologically-normal hippocampal samples from donors with no known brain diseases were obtained from the MRC Edinburgh Brain Bank (Edinburgh, UK) and the Queen Square Brain Bank (London, UK). Brain samples were disrupted and homogenized in an appropriate volume of QIAzol lysis reagent (Qiagen, Crawley, United Kingdom) by using a TissueRuptor handheld rotor-stator homogenizer (Qiagen, Crawley, United Kingdom). Total RNA was extracted from the homogenates using the RNeasy Lipid Tissue Mini Kit (Qiagen, Crawley, United Kingdom), according to the manufacturer’s instructions. RNA quality was examined by capillary electrophoresis on an Agilent Bioanalyzer 2100 (Agilent, Palo Alto, CA) and Agilent 2100 Expert software was used to calculate the RNA Integrity number (RIN) of each sample. Purity of the RNA sample was assessed using a NanoDrop1000 Spectrophotometer. Capillary electrophoresis traces were also examined. Samples with RNA integrity number scores (RIN) below 6, obvious RNA degradation, significant 18S or 28S ribosomal RNA degradation, ratio of absorbance at 260nm and 280nm <1.95, or with noticeable DNA or background contaminants did not pass QC, and were withheld from microarray analysis. The microarrays were processed at the Centre for Genomics Research in the University of Liverpool (http://www.liv.ac.uk/genomic-research/). 50ng of total RNA was amplified and labelled using the Agilent Low Input Quick Amp One-Colour Labeling Kit and labelled RNA was hybridized to Agilent SurePrint G3 Custom Exon 8x60K Microarrays designed to contain probes for each exon of 936 selected genes, including all known SLC genes. Standard Agilent protocols were followed. One array failed on five of the QC criteria and, hence, was excluded. Intensity data were extracted from the remaining arrays using the Feature Extraction Software, in line with the manufacturer’s recommendations. The uploaded files contain data both for a custom exon array designed to contain probes for each exon of 936 selected genes and for a custom gene expression array designed to contain gene expression probes for genes across the whole genome.

Dataset Information

Transcriptional interaction network analyses in dorsal nucleus of vagus nerve, locus coeruleus and substantia nigra in Parkinson's disease

Publications

Complex network-driven view of genomic mechanisms underlying Parkinson's disease: analyses in dorsal motor vagal nucleus, locus coeruleus, and substantia nigra.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets