Depression is a complex and heterogeneous disorder and a leading contributor to the global burden of of disease. Most previous research has focused on individual brain regions and individual genes that contribute to depression. However, emerging evidence in both humans and animal models suggests that dysregulated circuit function and gene expression across multiple brain regions drive depressive phenotypes. Here we use a bioinformatics approach intersecting differential expression analysis with weighted gene co-expression network analysis to identify transcriptional networks that regulate susceptibility to depressive-like symptoms in mice. We performed RNA-sequencing on multiple brain regions from control animals and those either susceptible or resilient to chronic social defeat stress (CSDS) at multiple time points after defeat. We bioinformatically identified several transcriptional networks that regulate depression susceptibility, and in vivo manipulations of these networks confirmed their functional significance at the levels of gene transcription, synaptic regulation, and behavior. Our findings reveal novel transcriptional networks that control stress susceptibility and offer fundamentally new leads for antidepressant drug discovery. Overall design: RNA-seq samples were generated from 4 brain regions (nucleus accumbens (NAC), prefrontal cortex (PFC), amygdala (AMY) and ventral hippocampus (VHIP) ) at 3 time-points (48h, 28d, 28d +1h stress) after chronic social defeat stress in control, susceptible and resilient mice. Additionally, RNA-seq samples were generated from virally infected VHIP tissue (HSV-GFP or HSV-Dkkl1) after an accelerated social defeat to assess the effect of Dkkl1 over-expression.
Circuit-wide Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulating Depression Susceptibility.
Specimen part, Cell line, Subject, Time
View SamplesIt is possible to identify the key genes and pathways involved in specific physiological processes using transcriptome analyses. However, these powerful new deep sequencing-based methods have rarely been applied to studies of memory function. We used the bow-tie maze to train rats by exposing them to highly familiar objects or to novel objects. Total RNA sequencing was then used to compare the transcriptome of the perirhinal cortices of naïve control rats and rats exposed to novel and familiar stimuli. Differentially expressed genes were identified between group Novel and group Familiar rats and these included genes coding for transcription factors and extracellular matrix-related proteins. Moreover, differences in alternative splicing were also detected between the two groups. To conclude, this study shows that RNA sequencing can be used as a tool to identify differences in gene expression in behaving animals undergoing the same task but encountering different exposures. Overall design: RNA profiles of perirhinal cortex from rats exposed to novel objects (n=5) or familiar objects (n=5) in a recognition memory task were investigated using the Ion Proton System. Controls were naïve rats that had not undergone any behavioural testing (n=4).
Recognition memory-induced gene expression in the perirhinal cortex: A transcriptomic analysis.
No sample metadata fields
View SamplesSamples used for hybridization consisted of non-pooled (NP) RNA extracts from 8 groups in each of two time periods after drug administration: oil vehicle treated control embryonic limb bud mesoderm and ectoderm, phosphate buffered saline vehicle control embryonic limb bud mesoderm and ectoderm, acetazolamide treated embryonic limb bud mesoderm and ectoderm, and cadmium sulfate treated embryonic limb bud mesoderm and ectoderm. Forty-eight hybridization experiments were on non-pooled (NP) individual RNA extracts.
Microarray analysis of murine limb bud ectoderm and mesoderm after exposure to cadmium or acetazolamide.
No sample metadata fields
View SamplesThe goal of this experiment was to examine the innate immune response to helminth infection in the lung. Hookworms (like many other helminths) use an obligate migration pathway through the lung. Their infection has been characterized in the gut in detail, but early immune responses in the lung have not been fully characterized.
Innate immune responses to lung-stage helminth infection induce alternatively activated alveolar macrophages.
No sample metadata fields
View SamplesProtein deficiency and intestinal parasite infection during pregnancy impair fetal growth through passage of signals from the maternal environment which signal impairment of fetal growth. The placenta is an important regulator of the transfer of these signals through differential expression of key placental genes. We used microarrays to examine placental gene expression responses to maternal protein deficiency (6% vs. 24% protein) and Heligmosomoides bakeri infection.
Expression of growth-related genes in the mouse placenta is influenced by interactions between intestinal nematode (Heligmosomoides bakeri) infection and dietary protein deficiency.
Specimen part
View SamplesThis study was undertaken in order to characterize the functions of Rex-1 and identify potential Rex-1 target genes.Both alleles of the Rex-1 gene were disrupted in J1 mouse embryonic stem cells. Gene expression levels in one of the resulting Rex-1 knockout cell lines was compared to that of J1 wild type cells.
Analysis of Rex1 (zfp42) function in embryonic stem cell differentiation.
No sample metadata fields
View SamplesTo uncover novel molecules involved in taste detection, we performed a microarray-based screen for genes enriched in taste neurons. Proboscis RNA from flies homozygous for a recessive poxn null mutation was compared to RNA from heterozygous controls. Poxn mutants have a transformation of labellar gustatory chemosensory bristles into mechanosensory bristles and therefore lack most or all taste neurons.
The molecular basis for water taste in Drosophila.
Sex
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrated approaches to miRNAs target definition: time-series analysis in an osteosarcoma differentiative model.
Specimen part, Cell line, Time
View SamplesMacrophage inflammatory protein 1alpha/CCL3 protein is a known pro-inflammatory cytokine that can mediate chemotaxis of monocytes and promote cell degranulation. Ccl3 gene expression is elevated in the CNS and visceral tissue of many lysosomal storage disorders. The deletion of Ccl3 in a mouse model of Sandhoff disease was reported to result in reduced monocyte-associated pathology in the brain, delayed neurodegeneration, and prolonged health. However, deletion of Ccl3 in a mouse model of Niemann-Pick C disease was dentrimental or neutral instead of beneficial. Prevention of neuronal loss was instead mediated by providing NPC1 to neurons.
Neuronal and epithelial cell rescue resolves chronic systemic inflammation in the lipid storage disorder Niemann-Pick C.
Specimen part
View SamplesWe explored the transcriptional modification induced by CD99 transfection in the osteosarcoma cell lines SaOS-2 after 0, 7 and 14 days in differentiation medium.
Integrated approaches to miRNAs target definition: time-series analysis in an osteosarcoma differentiative model.
Specimen part, Cell line, Time
View Samples