Neuropathic pain is an apparently spontaneous experience triggered by abnormal physiology of the peripheral or central nervous system, which evolves with time. Neuropathic pain arising from peripheral nerve injury is characterized by a combination of spontaneous pain, hyperalgesia and allodynia. There is no evidence of this type of pain in human infants or rat pups; brachial plexus avulsion, which causes intense neuropathic pain in adults, is not painful when the injury is sustained at birth. Since infants are capable of nociception from before birth and display both acute and chronic inflammatory pain behaviour from an early neonatal age, it appears that the mechanisms underlying neuropathic pain are differentially regulated over a prolonged postnatal period.
Differential regulation of immune responses and macrophage/neuron interactions in the dorsal root ganglion in young and adult rats following nerve injury.
Specimen part
View SamplesWe used microarray data to look for gene differentially expressed in the aorta of WT and L-PGDS ko male mice.
Lipocalin-Like Prostaglandin D Synthase but Not Hemopoietic Prostaglandin D Synthase Deletion Causes Hypertension and Accelerates Thrombogenesis in Mice.
Sex, Specimen part
View SamplesAustism spectrum disorder (ASD) is a heterogeneous behavioral disease most commonly characterized by severe impairment of social engagement and the presence of repetitive activities. The molecular etiology of ASD is still largely unknown despite a strong genetic component. Part of the difficulty in turning genetics into disease mechanisms and potentially new therapeutics is the sheer number and diversity of the genes that have been associated with ASD and ASD symptoms. The goal of this work is to use shRNA-generated models of genetic defects proposed as causative for ASD to identify the common pathways that might explain how they produce a common clinical outcome. Transcript levels of Mecp2, Mef2a, Mef2d, Fmr1, Nlgn1, Nlgn3, Pten, and Shank3 were knocked-down in mouse primary neuron cultures using shRNA/lentivirus constructs. Whole genome expression analysis was conducted for each of the knock-down cultures as well as a mock-transduced culture and a culture exposed to a lentivirus expressing luciferase. Gene set enrichment and a causal reasoning engine were employed to indentify pathway level perturbations generated by the transcript knock-down. Quantitation of the shRNA targets confirmed the successful knock-down at the transcript and protein levels of at least 75% for each of the genes. After subtracting out potential artifacts caused by transfection and viral infection, gene set enrichment and causal reasoning engine analysis showed that a significant number of gene expression changes mapped to pathways associated with neurogenesis, long-term potentiation, and synaptic activity. This work demonstrates that despite the complex genetic nature of ASD, there are common molecular mechanisms that connect many of the best established autism candidate genes. By identifying the key regulatory checkpoints in the interlinking transcriptional networks underlying autism, we are better able to discover the ideal points of intervention that provide the broadest efficacy across the diverse population of autism patients.
Transcriptomic analysis of genetically defined autism candidate genes reveals common mechanisms of action.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Peripheral blood gene expression changes during allergen inhalation challenge in atopic asthmatic individuals.
Sex, Age, Specimen part
View SamplesTo determine differential gene expression in peripheral blood of asthmatic individuals undergoing allergen inhalation challenge, post-challenge compared to pre-challenge
Peripheral blood gene expression changes during allergen inhalation challenge in atopic asthmatic individuals.
Sex, Age, Specimen part
View SamplesDetecting differential changes in the peripheral whole-blood transcriptome, post-challenge compared to pre-challenge; using non-globin reduced PAXgene (PAX.NGR) tubes
Peripheral blood gene expression changes during allergen inhalation challenge in atopic asthmatic individuals.
Sex, Age, Specimen part
View SamplesDetecting differential changes in the peripheral whole-blood transcriptome, post-challenge compared to pre-challenge; using globin reduced PAXgene (PAX.GR) tubes
Peripheral blood gene expression changes during allergen inhalation challenge in atopic asthmatic individuals.
Sex, Age, Specimen part
View SamplesMicroarray was used to identify differential gene expression pattern in Barrett's esophagus (BE), compared to the normal adjacent epithelia gastric cardia (GC) and normal squamous esophagus (NE)
Evidence for a functional role of epigenetically regulated midcluster HOXB genes in the development of Barrett esophagus.
Specimen part
View SamplesThe efficiency of central nervous system (CNS) remyelination declines with age. This is in part due to an age-associated decline in the phagocytic removal of myelin debris, which contains inhibitors of oligodendrocyte progenitor cell differentiation. In this study we show that expression of genes involved in the retinoid X receptor (RXR) pathway are decreased with aging in myelin-phagocytosing cells. Loss of RXR function in young macrophages mimics aging by delaying remyelination after experimentally-induced demyelination, while RXR agonists partially restore myelin debris phagocytosis in aged macrophages. The FDA-approved RXR agonist bexarotene, when used in concentrations achievable in human subjects, caused a reversion of the gene expression profile in aging human monocytes to a more youthful profile. These results reveal the RXR pathway as a positive regulator of myelin debris clearance and a key player in the age-related decline in remyelination that may be targeted by available or newly-developed therapeutics.
Retinoid X receptor activation reverses age-related deficiencies in myelin debris phagocytosis and remyelination.
Specimen part, Disease, Treatment
View SamplesAs rats do not develop neuropathic pain like hypersensitivity as neonates post nerve injury but do as adults we have used these arrays to help define the processes involved in this process.
T-cell infiltration and signaling in the adult dorsal spinal cord is a major contributor to neuropathic pain-like hypersensitivity.
Specimen part, Treatment
View Samples