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

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.

Interaction between the Corticotropin-Releasing Factor System and Hypocretins (Orexins): A Novel Circuit Mediating Stress Response

“…7). These results are consistent with the observation that high-arousal states, including stress, are associated with elevated hypocretin neurotransmission (Espana et al, 2003) and that acute stress increases levels of hypocretin mRNA (Reyes et al, 2003). A metabolic challenge (i.e., fasting) induces a robust activation of both hypocretinergic neurons and the postsynaptic targets of hypocretinergic axons , although this effect may also be attributed to stress.…”

Chemokines and chemokine receptors in the brain: implication in neuroendocrine regulation

“…Other chemokines such as MCP-1/CCL2 and growth-related gene alpha (GROa/ CXCL1) demonstrate a LPS responsiveness. Indeed, an up-regulation of MCP-1/CCL2 transcription is detected in the choroid plexus, CVO, blood vessels, and meninges (Thibeault et al 2001, Reyes et al 2003. GROa/CXCL1 also exhibits an up-regulation of its transcription in the PVN and the choroid plexus but not in the CVO (Reyes et al 2003).…”

“…Thus, IL-8/CXCL8 could be a component of a stress-related neuroendocrine system (Licinio et al 1992). Moreover, after a noxious stimulation consecutive to a s.c. injection of bacterial lipopolysaccharides (LPS), an up-regulation of CINC and interferon g-inducible protein (IP-10/ CXCL10) mRNAs expression was found in the PVN (Sakamoto et al 1996a, Reyes et al 2003. In addition, it was observed that IP-10/CXCL10 expression is also up-regulated following LPS in the circumventricular organs (CVO) including the subfornical organ (SFO) and the area postrema.…”

An inflammatory review of glucocorticoid actions in the CNS

“…Several recent microarray studies examined the effects of the high-affinity GR agonist dexamethasone on human PBMCs and found that amidst expected anti-inflammatory changes in gene expression, there were many proinflammatory systems such as chemokines, compliment proteins, and cytokines with increased expression (Galon et al 2002;Reyes et al 2003). The following section reviews several representative situations where acute GCs enhance peripheral inflammation, but is by no means comprehensive.…”