Project description:Parkinson's disease (PD) is the second most common neurodegenerative disease, involving the selecive death of dopaminergic neurons in the substantia nigra pars compacta brain region. Here, we performed next generation sequencing on RNA extracted from human substantia nigra tissue. The samples, acquired from the Netherland's Brain Bank, were taken post-mortem from PD and non-PD control donors. Analysis of the data revealed an upregulation of lncRNA LINC-PINT in PD substantia nigra. LINC-PINT interracts with the Polycomb Repressive Complex 2 (PRC2), inhibiting the tracription of multiple targets. Correspondingly, analysis of the data revealed that targets of PRC2 displayed larger disease-associated differences as compared to other genes, as well as enrichment for downregulation, suggesting that the differential expression of LINC-PINT in PD effects LINC-PINT/PRC2 interaction as well.
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.
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.
Project description:We report RNA sequencing results of human substantia nigra and putamen samples from Parkinson's disease patients and controls. Each substantia nigra sample is the result of pooling brain tissue from two individuals with the same , while each putamen sample is the result of pooling brain tissue from three individuals. We found 354 differentially expressed genes (DEGs) in the SN of PD patients compared to age-matched controls, while we observed 261 DEGs in the putamen samples. The top-enriched pathways from the SN were associated with “protein folding” and “neurotransmitter transport”, and the putamen DEGs with “synapse organization”. In summary, our data confirms the key role of protein folding and neuronal degeneration in the pathology of PD, and highlights new genes and pathways that have not yet been explored in the context of PD.
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.
Project description:Parkinson’s disease (PD) is the most common neurodegenerative movement disorder with unknown etiology. Loss of neuromelanin-containing dopaminergic (DA) neurons in the substanstia nigra (SN) is the hallmark of PD neuropathology. Here we performed single-nucleus RNA sequencing (snRNA-seq) of nuclei from the postmortem SN of control and idiopathic PD patients across various disease stages. The resulting transcriptomic atlas revealed a landscape of cellular alterations associated with disease progression in PD.
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 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.