Goal of the experiment: Analysis of gene expression changes in the cortex, striatum, hippocampus, hypothalamus, Drd2-MSNs and Drd1-MSNs of mice with a postnatal, neuron-specific ablation of GLP or G9a as compared to control mice.
Control of cognition and adaptive behavior by the GLP/G9a epigenetic suppressor complex.
Specimen part
View SamplesL-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 SamplesThe cellular heterogeneity of the brain confounds efforts to elucidate the biological properties of distinct neuronal populations.
A translational profiling approach for the molecular characterization of CNS cell types.
No sample metadata fields
View SamplesThe cellular heterogeneity of the brain confounds efforts to elucidate the biological properties of distinct neuronal populations.
A translational profiling approach for the molecular characterization of CNS cell types.
No sample metadata fields
View SamplesThe cellular heterogeneity of the brain confounds efforts to elucidate the biological properties of distinct neuronal populations.
A translational profiling approach for the molecular characterization of CNS cell types.
No sample metadata fields
View SamplesThe mechanisms by which the epidermis responds to disturbances in barrier function and restores homeostasis are unknown. With a disruption of the epidermal barrier, water is lost resulting in an increase in extracellular sodium concentration. We demonstrate that the sodium channel Nax functions as the sodium sensor. With increased extracellular sodium, Nax up-regulates prostasin which results in activation of the sodium channel ENaC, resulting in increased sodium flux and increased downstream mRNA synthesis of inflammatory mediators. The same pathways are present in lung epithelial cells.
Sodium channel Nax is a regulator in epithelial sodium homeostasis.
Sex, Specimen part, Cell line, Treatment, Time
View SamplesMicroRNA regulates protein expression of cells by repressing translation of specific target messenger transcripts. Loss of the neuron specific microRNA miR-128 in Dopamine D1-receptor expressing neurons in the murine striatum (D1-MSNs) lead to increased neuronal excitability, locomotor hyperactivity and fatal epilepsy.
MicroRNA-128 governs neuronal excitability and motor behavior in mice.
No sample metadata fields
View SamplesIntegrins facilitate intercellular movement and communication. Unlike the promiscuous activities of many integrins, 6 integrin is restricted to epithelia and partners exclusively with integrin V to modulate acute lung injury (ALI). Given that ALI is a complication of respiratory infection, we used mice lacking 6 integrin (6 KO) to probe the role of the epithelial layer in controlling the lung microenvironment during infection. We found 6 KO mice were protected from disease caused by influenza and Sendai virus infections. They were also protected from disease caused by Streptococcus pneumoniae infection alone and after prior influenza virus infection, the co-infection representing an often-lethal condition in humans. Resistance in the absence of epithelial 6 integrin was caused by intrinsic priming of the lung microenvironment by type I interferons through a mechanism involving transforming growth factor- regulation. Expression of 6 on epithelia suppresses the production of interferons, providing an advantage to the pathogen. Acute inhibition of 6 function may therefore provide a means to improve outcomes in lung microbial infections.
An Epithelial Integrin Regulates the Amplitude of Protective Lung Interferon Responses against Multiple Respiratory Pathogens.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identification of distinct changes in gene expression after modulation of melanoma tumor antigen p97 (melanotransferrin) in multiple models in vitro and in vivo.
Cell line
View SamplesMelanoma tumor antigen p97 or melanotransferrin (MTf) is an iron (Fe)-binding protein with high homology to serum transferrin. MTf is expressed at very low levels in normal tissues and in high amounts in melanoma cells. The over-expression of MTf in tumor cells was hypothesized to assist rapidly proliferating neoplastic cells with their increased Fe requirements. However, our recent characterization of the MTf knockout (MTf -/-) mouse demonstrated that MTf did not have an essential role in Fe metabolism. To understand the function of MTf, we utilized whole-genome microarray analysis to examine the gene expression profile of five models after modulating MTf expression. These models included two new stably transfected MTf hyper-expression models (SK-N-MC neuroepithelioma and LMTK- fibroblasts) and one cell type (SK-Mel-28 melanoma) where MTf was down-regulated by post-transcriptional gene silencing. These findings were compared to alterations in gene expression identified using the MTf -/- mouse. In addition, the changes identified from the gene array data were also assessed in a new model of MTf down-regulation in SK-Mel-2 melanoma cells. In the cell line models, MTf hyper-expression led to increased cellular proliferation, while MTf down-regulation resulted in decreased proliferation. Across all five models of MTf down- and up-regulation, we identified three genes modulated by MTf expression. These included ATP-binding cassette sub-family B member 5 (Abcb5), whose change in expression mirrored MTf down- or up-regulation. In addition, thiamine triphosphatase (Thtpa) and transcription factor 4 (Tcf4) were inversely expressed relative to MTf levels across all five models. The products of these three genes are involved in membrane transport, thiamine phosphorylation and cell proliferation/survival, respectively. This study identifies novel molecular targets directly or indirectly regulated by MTf and potential pathways involved in its function. These molecular targets could be involved, at least in part, to the role of MTf in modulating proliferation.
Identification of distinct changes in gene expression after modulation of melanoma tumor antigen p97 (melanotransferrin) in multiple models in vitro and in vivo.
Cell line
View Samples