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The Journal of Neuroscience, July 2, 2003, 23(13):5607-5616

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Categorically Distinct Acute Stressors Elicit Dissimilar Transcriptional Profiles in the Paraventricular Nucleus of the Hypothalamus

Teresa M. Reyes,¹ John R. Walker,² Casey DeCino,¹ John B. Hogenesch,² and Paul E. Sawchenko¹

¹Laboratory of Neuronal Structure and Function, The Salk Institute for Biological Studies, La Jolla, California 92037, and ²Genomics Institute of the Novartis Research Foundation, San Diego, California 92121

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 µg 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.

Key words: paraventricular; microarray; LPS; RST; orexin; chemokine

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Received Feb. 28, 2003; revised Apr. 10, 2003; accepted Apr. 21, 2003.

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