Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of paraventricular hypothalamic nucleus (PVH) from mice stimulated by either LPS injection or restraint to understand the molecular mechanisms in the modulation of PVH responses to categorically distinct stressors.

ABSTRACT: The paraventricular hypothalamic nucleus (PVH) is a key site for integrating neuroendocrine, autonomic, and behavioral adjustments to diverse homeostatic challenges, including physiological (e.g., infection or hemorrhage) and emotional [e.g., restraint (RST) or footshock] stresses. Both types of challenges ultimately converge to activate common response systems represented in PVH, including the hypothalamo-pituitary-adrenal axis and the sympathoadrenal system. Oligonucleotide microarrays (U74A; Affymetrix, Santa Clara, CA) were used to compare and contrast gene expression profiles in the PVH elicited at 1 and 3 hr after acute exposure to representative physiological [intraperitoneal injection of 10 microg lipopolysaccharide (LPS)] and emotional (30 min RST) stressors. In general, the two challenges recruited relatively few genes in common, with the degree of overlap varying across functional classes of genes. The greatest degree of commonality was seen among signaling molecules and neuropeptides, whereas transcription factors upregulated by RST and LPS were largely distinct. Unexpectedly, RST induced a number of immune-related molecules, which were not regulated by LPS. Hybridization histochemical analyses localized a subset of responsive transcripts to the PVH and/or immediately adjoining regions. Immunerelated molecules in particular distributed broadly to vascular and other barrier-associated cell types. These global transcriptional profiles inform the search for early (transcription factors) and late (target genes) mechanisms in the modulation of PVH, and generalized CNS, responses to categorically distinct stressors.

ORGANISM(S): Mus musculus

SUBMITTER: John Robert Walker

PROVIDER: E-GEOD-367 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Categorically distinct acute stressors elicit dissimilar transcriptional profiles in the paraventricular nucleus of the hypothalamus.

Reyes Teresa M TM Walker John R JR DeCino Casey C Hogenesch John B JB Sawchenko Paul E PE

The Journal of neuroscience : the official journal of the Society for Neuroscience 20030701 13

The paraventricular hypothalamic nucleus (PVH) is a key site for integrating neuroendocrine, autonomic, and behavioral adjustments to diverse homeostatic challenges, including "physiological" (e.g., infection or hemorrhage) and "emotional" [e.g., restraint (RST) or footshock] stresses. Both types of challenges ultimately converge to activate common response systems represented in PVH, including the hypothalamo-pituitary-adrenal axis and the sympathoadrenal system. Oligonucleotide microarrays (U7 ...[more]

PMID: 12843263

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Project description:This study explored how chronic stress influences the activity of signaling pathways that regulate inflammation in the human monocyte transcriptome. The sample consisted of 33 adults caring for a family member with glioblastoma, a terminal brain cancer, and 47 control subjects whose lives were free of major stressors. The subjects were assessed on four occasions across an eight-month period. Relative to controls, caregivers’ monocytes showed increased expression of genes bearing response elements for nuclear-factor kappa B, a key pro-inflammatory transcription factor in monocytes. Simultaneously, caregivers showed reduced expression of genes with response elements for the glucocorticoid receptor, a transcription factor that conveys anti-inflammatory signals to monocytes. These transcriptional disparities were not attributable to demographic or behavioral confounds. They also were not attributable to differences in diurnal cortisol output, or the abundance of glucocorticoid receptor expressed by monocytes. In ex vivo studies of monocytes stimulated with the bacterial product lipopolysaccharide, caregivers showed increased production of the pro-inflammatory cytokine interleukin-6, and were less sensitive to cortisol-mediated inhibition of this response. These findings suggest a scenario wherein chronic stressors engender functional changes that hamper monocytes’ capacity to transduce cortisol’s anti-inflammatory signals. These changes occur in parallel with, and perhaps enable, greater inflammatory signaling via nuclear-factor kappa B. The resulting inflammatory milieu could serve as a pathogenic mechanism through which chronic stressors like caregiving accentuate vulnerability to later health problems. series type: Risk prediction Individual differences in basal leukocyte gene expression profiles as a function of chronic caregiving stress Characteristics included in statistical analyses of gene expression data are provided in each sample records. Please note that educational attainment is scored as following; 0=less than high school, 1=high school diploma or equivalent, 2=associate's degree, 3=bachelor's degree, 4=masters degree, 5=doctoral degree

Dataset Information

Transcription profiling of paraventricular hypothalamic nucleus (PVH) from mice stimulated by either LPS injection or restraint to understand the molecular mechanisms in the modulation of PVH responses to categorically distinct stressors.

Publications

Categorically distinct acute stressors elicit dissimilar transcriptional profiles in the paraventricular nucleus of the hypothalamus.

Similar Datasets

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