Defining specific cell states of MPTP-induced Parkinson's disease by single-nucleus RNA sequencing
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA844884 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19522241_1.fastq.gz | Fastqsanger.gz | |||
| SRR19522241_2.fastq.gz | Fastqsanger.gz | |||
| SRR19522242_1.fastq.gz | Fastqsanger.gz | |||
| SRR19522242_2.fastq.gz | Fastqsanger.gz |
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Project description:Parkinson’s disease (PD), a neurodegenerative disease with the impairment of movement execution that is related to age, genetic and environmental factors. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyri-dine (MPTP) is a neurotoxin widely used to induce PD models, but the effect of MPTP on cell-gene of PD has not been fully elucidated. By single-nucleus RNA sequencing, we uncovered the PD-specific cells and revealed remarkable changes in their cellular states, including astrocytosis, endothelial cells absence, as well as a cluster of PD-exclusive medium spiny neuron cells. Furthermore, trajectory analysis of astrocyte and endothelial cells populations predicted candidate target gene sets that might be associated with PD. Notably, the detailed regulatory roles of astrocyte-specific transcription factors Dbx2 and Sox13 in PD were first revealed in our work. Finally, we characterized the cell-cell communications of PD-specific cells and found that the overall communication strength was enhanced in PD compared with matched control, especially the signaling pathways of NRXN and NEGR. Our work provides comprehensive overview on the changes of cellular states of the MPTP-induced mouse brain.
2022-08-10 | GSE205367 | GEO
Project description:Parkinson's disease (PD) is a neurodegenerative disease with an impairment of movement execution that is related to age and genetic and environmental factors. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin widely used to induce PD models, but the effect of MPTP on the cells and genes of PD has not been fully elucidated. By single-nucleus RNA sequencing, we uncovered the PD-specific cells and revealed the changes in their cellular states, including astrocytosis and endothelial cells' absence, as well as a cluster of medium spiny neuron cells unique to PD. Furthermore, trajectory analysis of astrocyte and endothelial cell populations predicted candidate target gene sets that might be associated with PD. Notably, the detailed regulatory roles of astrocyte-specific transcription factors Dbx2 and Sox13 in PD were revealed in our work. Finally, we characterized the cell-cell communications of PD-specific cells and found that the overall communication strength was enhanced in PD compared with a matched control, especially the signaling pathways of NRXN and NEGR. Our work provides an overview of the changes in cellular states of the MPTP-induced mouse brain.
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Project description:In Parkinson’s disease (PD), the progressive loss of substantia nigra dopamine cells has been associated with their vulnerability to oxidative stress, inflammation, and mitochondrial dysfunction. To identify multiple gene transcription alterations that may potentially underlie early stages of related degenerative processes in brain, we used the subcrhonic MPTP mouse model of PD and microarray analysis at 4 days post-MPTP when neurotoxic activity is maximal. Since PD results in gene changes throughout the brain, we assessed MPTP's effects in multiple regions: frontal cortex, striatum and midbrain. Keywords: neurotoxic response
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Project description:PD is the second most common neurodegenerative disease worldwide with growing prevalence. MPTP is a neurotoxin which causes the appearance of Parkinson's disease (PD) pathology. The involvement of the cholinergic system in PD has been identified decades ago and anti-cholinergic drugs were upon the first drugs used for symptomatic treatment of PD. Of note, MPTP intoxication is a model of choice for symptomatic neuroprotective therapies since it have been quite predictive. Mice were exposed to the dopaminergic neurotoxin 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), with or without the protective acetylcholinesterase (AChE-R) variant. Transgenic AChE-S (the synaptic variant), AChE-R (the shorter, protective variant) and FVB/N control mice were included in this study. Two brain regions were examined: the pre-frontal cortex (PFC) and the striatal caudate-putamen (CPu). Each condition (i.e brain region and transgenic variant) was examined on both naive and MPTP-exposed mice. 29 microarrays including hybridizations of control FVB/N PFC, control FVB/N CPu,control S transgenics PFC, control S transgenics CPu, control R transgenics PFC, control R transgenice CPu, MPTP FVB/N PFC, MPTP FVB/N CPu, MPTP S transgenics PFC, MPTP S transgenics CPu, MPTP R transgenics PFC and MPTP R transgenice CPu mRNA.
2012-01-09 | E-GEOD-31458 | biostudies-arrayexpress
Project description:PD is the second most common neurodegenerative disease worldwide with growing prevalence. MPTP is a neurotoxin which causes the appearance of Parkinson's disease (PD) pathology. The involvement of the cholinergic system in PD has been identified decades ago and anti-cholinergic drugs were upon the first drugs used for symptomatic treatment of PD. Of note, MPTP intoxication is a model of choice for symptomatic neuroprotective therapies since it have been quite predictive. Mice were exposed to the dopaminergic neurotoxin 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), with or without the protective acetylcholinesterase (AChE-R) variant. Transgenic AChE-S (the synaptic variant), AChE-R (the shorter, protective variant) and FVB/N control mice were included in this study. Two brain regions were examined: the pre-frontal cortex (PFC) and the striatal caudate-putamen (CPu). Each condition (i.e brain region and transgenic variant) was examined on both naive and MPTP-exposed mice.
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Project description:Irisin, a recently identified myokine, is increased by exercise and plays pivotal roles in energy metabolism. However, it remains unknown whether irisin has any protective effects on Parkinson's disease. To examine the role of irisin in PD, irisin was peripherally delivered before or after the establishment of PD models by MPTP to explore its effect. We performed mRNA analysis in the midbrain of MPTP treated mice with irisin pre-treatment or delayed-treatment through RNA-Sequencing. And bioinformatic analysis was done on the identified deregulated genes through gene ontology (GO) analysis, KEGG pathway analysis and Gene set enrichment analysis (GSEA). Pathway analysis indicated that NAD(P)H activity and metabolism, PI3K-AKT pathway, MAPK pathway, inflammation-related signaling pathways played vital roles in the treatment of MPTP treated mice by irisin pre-treatment and irisin delayed treatment. This study provides a detailed analysis of the effects and underlying mechanisms of irisin treatment in MPTP treated mice.
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Project description:RNAseq was performed on caudate, putamen, and substantia nigra samples from animals treated with MPTP to induce a Parkinson's-like condition, and then transplanted with hpNSCs or control buffer. The goal of the study was to determine if there were any difference in gene expression caused by the transplanted cells.
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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.
2009-12-31 | E-GEOD-17542 | biostudies-arrayexpress
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.
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