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Corticotropin-releasing factor and glucocorticoid receptor (GR) gene expression in the paraventricular nucleus of immune-challenged transgenic mice expressing type II GR antisense ribonucleic acid

Journal of Molecular Neuroscience volume 8, pages 165–179 (1997)Cite this article

Abstract

The purpose of this study was to investigate the effect of the immune activator lipopolysaccharide (LPS) on the expression of corticotropin-releasing factor (CRF) and glucocorticoid receptor (GR) mRNA in the paraventricular nucleus (PVN) of transgenic mice with impaired GR function caused by endogenous expression of GR antisense RNA. At 3 and 8 wk of age, control and transgenic mice were sacrificed 4.5 h after a single ip administration of LPS (100 µg/100 g of body wt) or vehicle. Frozen brains were mounted on a microtome and cut in 20-µm sections. mRNAs encoding CRF and GR were assayed byin situ hybridization histochemistry using35S-labeled riboprobes, and localization of Fos-immunoreactive (Fos-ir) nuclei was determined by immunocytochemistry. Basal expression of CRF mRNA in the PVN, central nucleus of the amygdala (CeA), and geniculate complex (GN) was similar in the control and transgenic mice. LPS induced a comparable neuronal activation in the PVN of control and transgenic mice as revealed by the number of Fos-ir neurons. Moreover, the endotoxin caused a significant increase in the CRF mRNA levels within the PVN and CeA, an effect observed in both animal models. The endotoxin did not notably modulate CRF expression in other regions, such as GN. Although GR mRNA was expressed in the PVN of control mice under basal conditions, this transcript was not detected in this hypothalamic structure in LPS-treated and transgenic animals. This indicated that endogenous Type II GR mRNA is decreased in the PVN of mice expressing Type II GR antisense RNA and that gene is downregulated by LPS. Hybridization signal for CRF and GR transcripts was not notably altered by the age of mice. These results provide evidence that the basal expression of CRF and the increase of neuroendocrine CRF transcription in response to immunogenic challenges are not significantly affected by impairment of the Type II GR function.

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  1. Laboratory of Molecular Endocrinology, CHUL Research Center and Department of Physiology, Laval University, 2705, boul. Laurier, G1V 4G2, Québec, Canada

    Nathalie Laflamme & Serge Rivest

  2. Laboratory of Neuroscience, CHUL Research Center and Department of Physiology, Laval University, 2705, boul. Laurier, G1V 4G2, Québec, Canada

    Nicholas Barden

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  1. Nathalie Laflamme
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Laflamme, N., Barden, N. & Rivest, S. Corticotropin-releasing factor and glucocorticoid receptor (GR) gene expression in the paraventricular nucleus of immune-challenged transgenic mice expressing type II GR antisense ribonucleic acid. J Mol Neurosci 8, 165–179 (1997). https://doi.org/10.1007/BF02736831

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Index Entries

  • Acute-phase response
  • antisense knockdown technology
  • c-fos
  • endotoxin
  • HPA axis
  • neuroendocrinology
  • glucocorticoids
  • in situ hybridization
  • immunocytochemistry
  • stress