Rattus norvegicus
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ABSTRACT:
PROVIDER: PRJNA358380 | ENA |
REPOSITORIES: ENA
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Project description:N27 cells are dopaminergic neurons derived from rat midbrain and are extensively employed as a model for neurodegeneration. N27 cells were challenged with 2 neurotoxins associated with Manganism (Manganese Chloride;Mn) and Parkinson's Disease (1-methyl-4-phenylpyridinium ion;MPP+). Mn and MPP+ result in movement dysfunction and are mitochondrial toxins particularly affecting complexes I.This study aimed to understand and differentiate the molecular mechanisms underlying Mn and MPP+ mediated dopaminergic insult by evaluating the differential gene expression pattern in the two models
2017-10-04 | GSE92963 | GEO
Project description:Idiopathic Parkinson’s disease (iPD) and manganese-induced atypical Parkinsonism are characterized by movement disorder and nigrostriatal pathology. Although clinical features, brain region involved and responsiveness to L-DOPA differentiate both, the differences at the neuronal level are largely unknown. We investigated the morphological, physiological and molecular differences in dopaminergic neurons exposed to the PD toxin 1-methyl-4-phenylpyridinium ion (MPP+) and manganese (Mn). While Mn was neurotoxic at lower dose, MPP+ toxicity entailed oxidative damage, mitochondria dysfunction and glycolytic shift. Morphological analysis highlighted mitochondrial damage, while morphometric analysis indicated loss of neuronal processes in the MPP+ model and not in the Mn model. Elecrophysiological analysis demonstrated lower number of spikes and firing frequency in MPP+ treated cells, while it was unchanged in the Mn model. High throughput transcriptomic analysis revealed upregulation of 694 and 603 genes and down-regulation of 428 and 255 genes in the MPP+ and Mn models respectively. Many differentially expressed genes were unique to either models and contributed to neuroinflammation, metabolic and mitochondrial function, apoptosis and nuclear function, synaptic plasticity, neurotransmission and cytoskeletal architecture. Analysis of the JAK-STAT pathway with implications for neuritogenesis, neuronal proliferation and nuclear function revealed contrasting profile between Mn and MPP+ models. Genome-wide DNA methylation profile revealed significant differences between both models and substantiated the epigenetic basis of the difference in the JAK-STAT pathway. We conclude that iPD and atypical Parkinsonism represent a divergent neurotoxicological manifestation at the dopaminergic neuronal level with implications for pathobiology and to evolve novel therapeutics
2017-10-04 | GSE92691 | GEO
Project description:experiment in midbrain primary cultures, enriched in dopaminergic neurons
| PRJNA94469 | ENA
Project description:Parkinson's disease (PD) listed as the second most common neurodegenerative disease. 2-[[(1,1-Dimethylethyl)oxidoimino]-methyl]-3,5,6-trimethylpyrazine (TBN), a novel nitrone derivative of tetramethylpyrazine, has shown benefits for the treatment both in vitro and in vivo, TBN protects and rescues dopaminergic neurons from MPP(+) and MPTP/6-OHDA-induced damage by reducing ROS and increasing cellular antioxidative defense capability. Here, we investigate the proteome changes in the 6-OHDA induced PD rat model and the rescue effects after treated by TBN.
2022-03-02 | PXD004812 | Pride
Project description:Comparison of SNc and VTA dopaminergic neurons. Greene-5P50NS038399-050001
| PRJNA90563 | ENA
Project description:Gene expression profile of neurotoxin exposure in rat midbrain dopaminergic neurons
| PRJNA359180 | ENA
Project description:The Cellular and Genomic Response of Dopaminergic Neurons (N27) to Commericial “Capped” Nanosilver
| PRJNA208894 | ENA
Project description:Previous studies demonstrated that dopaminergic neurons in the substantia nigra pars compacta (SNpc) of mice with null mutations for genes encoding a-synuclein and/or y-synuclein are resistant to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity. An original straightforward interpretation of these results was that these proteins are directly involved in the mechanism of MPTP-induced degeneration and this view has become commonly accepted. Here we provide evidence that a plausible explanation of this resistance is not the absence of these synucleins per se but their substitution on the membrane of synaptic vesicles by the third member of the family, b-synuclein. Dopaminergic neurons of mice lacking b-synuclein singularly or in combination with the loss of other synucleins, were sensitive to the toxic effect of MPTP. Dopamine uptake by synaptic vesicles isolated from the striatum of triple a/b/y-synuclein deficient mice was significantly reduced, while reintroduction of b-synuclein either in vivo or in vitro reversed this effect. Proteomic analysis of complexes formed on the surface of synuclein-free synaptic vesicles after addition of recombinant b-synuclein identified multiple integral constituents of these vesicles as well as typically cytosolic proteins, including key enzymes involved in dopamine synthesis, tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC). Therefore, b-synuclein plays a scaffolding role for the assembly of molecular complexes that enhance the ability of synaptic vesicles to uptake and sequester dopamine and other structurally similar molecules, including MPP+. Deficiency of b-synuclein therefore results in the accumulation of MPP+ in the cytosol, where it imposes a damaging effect on presynaptic terminals and ultimately the destruction of dopaminergic neurons.
2021-11-29 | PXD027667 | Pride
Project description:Mutant TDP-43 in Astrocytes Kills Motor Neurons in Rats through Neurotoxic Gain and Neuroprotective Loss in Astrocytes
| PRJNA179143 | ENA
Project description:Advances in stem cell technologies open up new avenues for modelling development and diseases. The success of these pursuits however rely on the use of cells most relevant to those targeted by the disease of interest, for example, midbrain dopaminergic neurons for Parkinson’s disease. In the present study, we report the generation of a human induced pluripotent stem cell (iPSC) line capable of purifying and tracing nascent midbrain dopaminergic progenitors and their differentiated progeny via the expression of a Blue Fluorescent Protein (BFP). This was achieved by CRISPR/Cas9 assisted knock-in of BFP and Cre into the safe harbour locus AAVS1 and an early midbrain dopaminergic lineage marker gene LMX1A, respectively. Immunocytochemical analysis and single cell RNA sequencing of iPSC-derived neural cultures confirms developmental recapitulation of the human fetal midbrain and high quality midbrain cells. By modelling Parkinson’s disease-related drug toxicity using 1-Methyl-4-phenylpyridinium (MPP+), we showed preferential reduction of BFP+ cells, a finding demonstrated independently by cell death assays and single cell transcriptomic analysis of MPP+ treated neural cultures. Together, these results highlight the importance of disease relevant cell type in stem cell modelling.
2023-11-24 | GSE247600 | GEO