L-3,4-dihydroxyphenylalanine (levodopa) treatment is the major pharmacotherapy for Parkinson's disease. However, almost all patients receiving levodopa eventually develop debilitating involuntary movements (dyskinesia). While it is known that striatal spiny projection neurons (SPNs) are involved in the genesis of this movement disorder, the molecular basis of dyskinesia is not understood. In this study, we identify distinct cell-type-specific gene expression changes that occur in sub-classes of SPNs upon induction of a parkinsonian lesion followed by chronic levodopa treatment. We identify several hundred genes whose expression is correlated with levodopa dose, many of which are under the control of AP-1 and ERK signaling. In spite of homeostatic adaptations involving several signaling modulators, AP-1-dependent gene expression remains highly dysregulated in direct pathway SPNs (dSPNs) upon chronic levodopa treatment. We also discuss which molecular pathways are most likely to dampen abnormal dopaminoceptive signaling in spiny projection neurons, hence providing potential targets for antidyskinetic treatments in Parkinson's disease.
Molecular adaptations of striatal spiny projection neurons during levodopa-induced dyskinesia.
Specimen part, Treatment
View SamplesWe wanted to determine how type II versus type III Toxoplasma infection affect host gene expression
Toxoplasma polymorphic effectors determine macrophage polarization and intestinal inflammation.
Cell line
View SamplesWe wanted to determine how type I ROP16 affect host gene expression
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Specimen part
View SamplesEbf1 is a transcription factor with documented, and dose dependent, functions in both normal and malignant B-lymphocyte development. In order to understand more about the role of Ebf1 in malignant transformation, we have investigated the impact of reduced functional Ebf1 dose on early B-cell progenitors. Gene expression analysis in loss and gain of function analysis suggested that Ebf1 was involved in the regulation of genes of importance for DNA repair as well as cell survival. Investigation of the level of DNA damage in steady state as well as after induction of DNA damage by UV light supported that pro-B cells lacking one functional allele of Ebf1 display a reduced ability to repair DNA damage. This was correlated to a reduction in expression of Rad51 and combined analysis of published 4C and chromatin Immuno precipitation data suggested that this gene is a direct target for Ebf1. Even though the lack of one allele of Ebf1 did not result in any dramatic increase of tumor formation, we noted a dramatic increase in the formation of pro-B cell leukemia in mice carrying a combined heterozygote mutation in the Ebf1 and Pax5 genes. Even though the tumors were phenotypically similar and stable, we noted a large degree of molecular heterogeneity well in line with a mechanism involving impaired DNA repair. Our data support the idea that Ebf1 controls homologous DNA repair in a dose dependent manner and that this may explain the frequent involvement of Ebf1 in human leukemia
Ebf1 heterozygosity results in increased DNA damage in pro-B cells and their synergistic transformation by Pax5 haploinsufficiency.
Specimen part, Cell line, Time
View SamplesGarlic is a popular flavor enhancer in modern cuisines. Although anti-atherosclerotic, anti-proliferative, hypolipidemic and chemopreventative effects of garlic are known for a long time, the mechanisms of garlic as a dietary supplement ramain largely unknown.
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View SamplesThe inflammatory response plays out over time in a reproducible and organized manner after an initiating stimulus. Here we showed that the genes activated in cultured mouse fibroblasts in response to the proinflammatory cytokine tumor necrosis factorcan be divided roughly into three groups, each with different induction kinetics. Whereas differential transcription is important in determining the grouping of these genes, differential mRNA stability also exerted strong influence in some cases overriding that of transcriptional control elements on the temporal order of gene expression. mRNA transcripts expressed early after TNF stimulation have abundant AU-rich elements in their 3'-untranslated regions whereas those expressed later are contain fewer AU-rich sequences. Thus mRNA stability and transcriptional control, two intrinsic characteristics of genes, control the kinetics of proinflammatory cytokine-induced gene expression.
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No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
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Sex, Specimen part
View SamplesWe performed gene-expression analysis of mouse Purkinje cells as a model single-type neuron. DNA microarray analysis detected at least 7,055 genes in Purkinje cells, most of which are classified into functional molecule categories.
No associated publication
Sex, Specimen part
View SamplesWe performed gene-expression analysis of mouse cerebellar granule cell layer as compared to that of Purkinje cells. DNA microarray analysis detected genes in cerebellar granule cell layer, most of which are classified into functional molecule categories.
No associated publication
Sex, Specimen part
View SamplesDomesticated animal populations often show profound reductions in predator avoidance and fear-related behavior compared to wild populations. These reductions are remarkably consistent and have been observed in a diverse array of taxa including fish, birds, and mammals. Experiments conducted in common environments indicate that these behavioral differences have a genetic basis. In this study, we quantified differences in fear-related behavior between wild and domesticated zebrafish strains and used microarray analysis to identify genes that may be associated with this variation.
Brain transcriptome variation among behaviorally distinct strains of zebrafish (Danio rerio).
Sex, Specimen part
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