Immune challenge and immobilization stress induce transcription of the gene encoding the CRF receptor in selective nuclei of the rat hypothalamus

S. Rivest, N. Laflamme, R. E. Nappi

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The present study investigated the effect of intraperitoneal (i.p.) administration of endotoxin lipopolysaccharide (LPS) and immobilization stress on the genetic expression of corticotropin-releasing factor receptor (CRF-R) in the brains of conscious male Sprague-Dawley rats. One group of rats was killed at 1, 3, 6, 9, and 12 hr after a single intraperitoneal injection of either the LPS (250 μg/100 gm of body weight) or the vehicle solution; the other group was killed before, immediately after, 1.5, 3, 6, and 12 hr after a 90 min acute session of immobilization stress. Rats were deeply anesthetized and rapidly perfused with a solution of 4% paraformaldehyde-borax. Frozen brains were mounted on a microtome and cut from the olfactory bulb to the medulla in 30 μm coronal sections. mRNA encoding the rat CRF-R was assayed by in situ hybridization histochemistry using a 35S-labeled riboprobe, and CRF-R localization within CRF- immunoreactive neurons in the PVN was determined using a combination of immunocytochemistry and in situ hybridization techniques. Strong basal levels of CRF-R transcripts were observed in several regions of the brain (piriform cortex, medial and basolateral nuclei of the amygdala, red nucleus, pontine gray, cerebellum, laterodorsal tegmental nucleus, caudal division of the zona incerta, nucleus incertus, spinal and principal sensory nuclei of the trigeminal nerve, and various layers of the cortex). A low to moderate signal was also detected in multiple sites (medial septal nucleus, nucleus of the diagonal band, supraoptic nucleus, arcuate nucleus of the hypothalamus, interpeduncular nucleus, and nucleus prepositus). Whereas vehicle-treated and control rats displayed hardly detectable signals of CRF-R mRNA in the paraventricular nucleus (PVN), CRF-R gene transcription was highly stimulated by LPS administration and immobilization stress in this hypothalamic structure. Indeed, the CRF-R mRNA signal was positive in the dorsomedial parvocellular PVN 3 hr after LPS injection, strong and maximum in both parvo- and magno-PVN at 6 hr postinjection, and declined 9 and 12 hr after treatment. Similarly, 90 min and 3 hr after the immobilization session, mRNA encoding the CRF-R was highly expressed in the parvo-PVN and totally vanished 12 hr after the stress. A lower but significant increase in the CRF-R transcript signal was also observed in the supraoptic nucleus 6 hr after the LPS treatment. Systemic endotoxin and immobilization stress did not modulate the expression of CRF-R gene in other regions, which suggests that these types of challenges can induce a highly selective activation of CRF-R within hypothalamic nuclei directly involved in the regulation of neuroendocrine functions. CRF-immunoreactive neurons of the parvo-PVN expressed the CRF-R transcript after both the stress and the systemic LPS administration. Thus, CRF may play a role as neuromodulator, controlling directly the activity of neuroendocrine CRF motoneurons during immune challenge and other stressful circumstances for the organism.

Original languageEnglish
Pages (from-to)2680-2695
Number of pages16
JournalJournal of Neuroscience
Issue number4
Publication statusPublished - 1995


  • corticotropin-releasing factor
  • hypothalamic-pituitary-adrenal axis
  • immune response
  • immunocytochemistry
  • in situ hybridization histochemistry
  • male rats
  • neuroendocrinology
  • paraventricular nucleus of the hypothalamus
  • supraoptic nucleus of the hypothalamus

ASJC Scopus subject areas

  • Neuroscience(all)


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