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Journal of Neuroscience, Vol 15, 2680-2695, Copyright © 1995 by Society for Neuroscience
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 and RE Nappi
Laboratory of Molecular Endocrinology, CHUL Research Center, Quebec, Canada.
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 micrograms/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 microns 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.(ABSTRACT TRUNCATED AT 400 WORDS)
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