The goal of the experiments was to profile and analyze gene activity during murine pre-implantation development. Samples were collected at twelve time points from the germinal vesicle (GV) stage oocyte to the late (expanded) blastocyst.
A genome-wide study of gene activity reveals developmental signaling pathways in the preimplantation mouse embryo.
Age
View SamplesDisruption of local iron homeostasis is a common feature of neurodegenerative diseases. We focused on dopaminergic neurons, asking how iron transport proteins modulate iron homeostasis in vivo. Inactivation of the transmembrane iron exporter ferroportin had no apparent consequences. However, loss of the transferrin receptor 1, involved in iron uptake, caused profound, age-progressive neurodegeneration with features similar to Parkinsons disease. There was gradual loss of dopaminergic projections in the striatum with subsequent death of dopaminergic neurons in the substantia nigra. After depletion of 30% of the neurons the mice developed neurobehavioral parkinsonism, with evidence of mitochondrial dysfunction and impaired mitochondrial autophagy. Molecular analysis revealed strong signatures indicative of attempted axonal regeneration, a metabolic switch to glycolysis and the unfolded protein response. We speculate that cellular iron deficiency may contribute to neurodegeneration in human patients
Altered dopamine metabolism and increased vulnerability to MPTP in mice with partial deficiency of mitochondrial complex I in dopamine neurons.
Age, Specimen part
View SamplesDifferential gene expression as a consequence of PTCD1 loss Overall design: We used RNA from control and PTCD1 knockout mice to investigate changes at the RNA level in response to PTCD1 loss
PTCD1 Is Required for 16S rRNA Maturation Complex Stability and Mitochondrial Ribosome Assembly.
Specimen part, Subject
View SamplesFTY720/Fingolimod, an FDA-approved drug for treatment of multiple sclerosis, has beneficial effects in the CNS that are not yet well understood, independent of its effects on immune cell trafficking. Here we show that FTY720 enters the nucleus where it is phosphorylated by sphingosine kinase 2 (SphK2) and nuclear FTY720-P that accumulates there, binds and inhibits class I histone deacetylases (HDACs) enhancing specific histone acetylations. FTY720 is also phosphorylated in mice and accumulates in various brain regions, including hippocampus, inhibits HDACs and enhances histone acetylation and gene expression programs associated with memory and learning leading to improvement of memory impairment independently of its immunosuppressive actions. Our data suggest that sphingosine-1-phosphate and SphK2 play specific roles in memory functions and that FTY720 may be a useful adjuvant therapy to facilitate extinction of aversive memories.
Active, phosphorylated fingolimod inhibits histone deacetylases and facilitates fear extinction memory.
Sex, Age, Specimen part, Treatment
View SamplesFyn kinase has been implicated in multiple behavioral responses to ethanol and in the regulation of myelin gene expression. Here we tested whether Fyn kinase modulated basal or ethanol-responsive expression of genes regulated by acute ethanol in brain regions of the mesolimbocortical dopamine pathway.
Fyn-dependent gene networks in acute ethanol sensitivity.
Sex, Age, Specimen part, Treatment
View SamplesHuman lung cancer (A549) cells were treated 50uM of the metal cation-containing chemotherapeutic drug motexafin gadolinium (MGd) for 4, 12, and 24 hrs and expression compared to control cells (treated with 5% mannitol for the same length of time)
Motexafin gadolinium disrupts zinc metabolism in human cancer cell lines.
No sample metadata fields
View SamplesPersistent changes in brain gene expression are hypothesized to underlie thealtered neural signaling producing abusive consumption in AUD. To identify brain regional gene expression networks contributing to progressive ethanol consumption, we performed microarray and scale-free network analysis of expression responses in a C57BL/6J mouse model utilizing chronic intermittent ethanol by vapor chamber (CIE) in combination with limited access oral ethanol consumption.
Brain regional gene expression network analysis identifies unique interactions between chronic ethanol exposure and consumption.
Sex
View SamplesComparison of sense (forward probes) and antisense (reverse probes on U74 v1 gene arrays) transcripts in mouse kidney and brain.
Expression profiling of antisense transcripts on DNA arrays.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Time-Course Analysis of Brain Regional Expression Network Responses to Chronic Intermittent Ethanol and Withdrawal: Implications for Mechanisms Underlying Excessive Ethanol Consumption.
Sex, Specimen part
View SamplesLasting behavioral and physiological changes such as abusive consumption, dependence, and withdrawal are characteristic features of alcohol use disorders (AUD). Mechanistically, persistent changes in gene expression are hypothesized to contribute to these brain adaptations leading to ethanol toxicity and abuse. Here we employed repeated chronic intermittent ethanol (CIE) exposure by vapor chamber as a mouse model to simulate the cycles of ethanol exposure and withdrawal commonly seen with AUD. This model has previously been shown to induce progressive ethanol consumption in rodents. Brain regional expression networks contributing to CIE-induced behavioral changes were identified by microarray analysis across five brain regions in the mesolimbic dopamine system and extended amygdala with tissue harvested from 0-120 hours following the last cycle of CIE. Weighted Gene Correlated Network Analysis (WGCNA) was used to identify gene networks over-represented for CIE-induced temporal expression changes across brain regions. Differential gene expression analysis of CIE vs. air-treated controls showed that long-lasting gene regulation occurred 5-days after the final cycle of ethanol exposure only in prefrontal cortex (PFC) and hippocampus. In the majority of brain-regions, however, ethanol regulated gene expression changes occurred only immediately following CIE or within the first 8-hours of removal from ethanol.
Time-Course Analysis of Brain Regional Expression Network Responses to Chronic Intermittent Ethanol and Withdrawal: Implications for Mechanisms Underlying Excessive Ethanol Consumption.
Sex, Specimen part
View Samples