Whole Transcriptome Analysis of Substantia Nigra in Mice with MPTP-Induced Parkinsonism Bearing Defective Glucocerebrosidase Activity
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PROVIDER: PRJEB64926 | ENA |
REPOSITORIES: ENA
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Project description:We characterized the transcriptomic profiles of cells from the substantia nigra (SN) of mice with co-injection with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and selective inhibitor of GCase activity (conduritol-β-epoxide, (CBE)) to mimic PD bearing GCase dysfunction (MPTP+CBE), mice treated with MPTP, mice treated with CBE and control mice treated with injec-tion of sodium chloride (NaCl) (vehicle).
2023-08-31 | E-MTAB-13244 | biostudies-arrayexpress
Project description:Parkinson’s disease (PD) is a representative neurodegenerative disease that is characterized the death of dopamine-generating cells in the substantia nigra (SN). Acupuncture stimulations at GB34 and LR3 resulted in the enhanced survival of dopaminergic neurons in the SN in the parkinsonism animal models. SN is known as an important player in brain function, in particular, movement. Behavioral tests showed that acupuncture stimulations improved the motor dysfunction in a previous study by almost 87.7%. This study investigated the changes of gene expression profiles in the SN regions of the relatively chronic parkinsonism model and demonstrated the genes that may be related to the inhibitory effect of acupuncture on the change in gene expression in the SN induced by an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication using a whole transcript array. We investigated gene expression profile changes in the substantia nigral region of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism models after acupuncture at the acupoints GB34 and LR3
2014-12-27 | GSE48293 | GEO
Project description:Mutations in the GBA1 gene represent the major genetic risk factor for Parkinson's disease (PD). The lysosomal enzyme beta-glucocerebrosidase (GCase) encoded by the GBA1 gene participates in both the endolysosomal pathway and the immune response. Disruption of these mechanisms is involved in PD pathogenesis. However, molecular mechanisms of PD associated with GBA1 mutations (GBA-PD) are unknown today in particular due to the partial penetrance of GBA1 variants in PD. The modifiers of GBA1 penetrance have not been elucidated. We characterized the transcriptomic profiles of cells from the substantia nigra (SN) of mice with co-injection with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and selective inhibitor of GCase activity (conduritol-β-epoxide, (CBE)) to mimic PD bearing GCase dysfunction (MPTP+CBE), mice treated with MPTP, mice treated with CBE and control mice treated with injection of sodium chloride (NaCl) (vehicle). Differential expression analysis, pathway enrichment analysis, and outlier detection were performed. Functional clustering of differentially represented transcripts revealed more processes associated with the functioning of neurogenesis, inflammation, apoptosis and autophagy in MPTP+CBE and MPTP mice than in vehicle mice, with a more pronounced alteration of autophagy processes in MPTP+CBE mice than in MPTP mice. The PI3K-Akt-mTOR signaling pathway may be considered a potential target for therapy in PD with GCase dysfunction.
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Project description: Not available
| S-BSST1159 | biostudies-other
Project description:To explore effect of medium-chain triglyceride KD (MCT-KD) in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model, we profiled substantia nigra pars compacta tissues from control group, MPTP group and MPTP + KD mice by RNA sequencing (RNA-seq).
2023-08-01 | GSE232039 | GEO
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
Project description:Acupuncture at acupoints GB34 and LR3 has been reported to inhibit nigrostriatal degeneration in parkinsonism models, yet the genes related to this preventive effect of acupuncture on the nigrostriatal dopaminergic system remain elusive. We investigated gene expression profile changes in the striatal region of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism models after acupuncture at the acupoints GB34 and LR3 C57BL/6 mice were divided into four experimental groups; â C: Control, â¡ M: MPTP-treatment only, ⢠MA: MPTP- and acupuncture-treatment at acupoints GB34 and LR3, ⣠MNA: MPTP- and acupuncture-treatment at non-acupoints. Total RNA was isolated from two brains' striatal regions of each experimental group (4 experimental group à 2 samples of each experimental group = total 8 samples).
2010-10-23 | E-GEOD-24829 | biostudies-arrayexpress
Project description:Acupuncture stimulations at GB34 and LR3 inhibit the reduction of tyrosine hydroxylase in the nigrostriatal dopaminergic neurons in the parkinsonism animal models. Especially, behavioral tests showed that acupuncture stimulations improved the motor dysfunction in a previous study. The thalamus is a crucial area for the motor circuit and has been identified as one of the most markedly damaged areas in Parkinson’s disease (PD), so acupuncture stimulations might also have an effect on the thalamic damage. We investigated gene expression profile changes in the thalamic region of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism models after acupuncture at the acupoints GB34 and LR3 C57BL/6 mice were divided into four experimental groups; ① C: Control, ② M: MPTP-treatment only, ③ MA: MPTP- and acupuncture-treatment at acupoints GB34 and LR3, ④ MNA: MPTP- and acupuncture-treatment at non-acupoints. Total RNA was isolated from two brains' thalamic regions of each experimental group (4 experimental group × 2 samples of each experimental group = total 8 samples).
2012-01-18 | E-GEOD-35138 | biostudies-arrayexpress
Project description:Acupuncture at acupoints GB34 and LR3 has been reported to inhibit nigrostriatal degeneration in parkinsonism models, yet the genes related to this preventive effect of acupuncture on the nigrostriatal dopaminergic system remain elusive. We investigated gene expression profile changes in the striatal region of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism models after acupuncture at the acupoints GB34 and LR3
2010-10-23 | GSE24829 | GEO
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