Submitted on March 29, 2004
Accepted on June 1, 2004
NEURONAL ACTIVITY AND CRF RECEPTOR GENE TRANSCRIPTION IN THE BRAINS OF RATS WITH COLITIS
Christophe Porcher1, Valerie Sinniger2, Aurelie Juhem1, Patrick Mouchet1, and Bruno Bonaz2*
1 Groupe d'Etude du Stress et des Interactions Neuro-Digestives (EA3744), Hopital Albert Michallon, Centre Hospitalier Universitare, Grenoble, France
2 Groupe d'Etude du Stress et des Interactions Neuro-Digestives (EA3744), Hopital Albert Michallon, Centre Hospitalier Universitare, Grenoble, France; Departement d'Hepato-Gastroenterologie, Hopital Albert Michallon, Centre Hospitalier Universitare, Grenoble, France
* To whom correspondence should be addressed. E-mail: Bruno.Bonaz{at}ujf-grenoble.fr.
We aimed to characterize neuronal and corticotrophin-releasing factors (CRF) pathways at
the acute phase of a model of colitis in rats. Male rats received an intracolonic injection of either
vehicle (controls) or trinitrobenzenesulfonic acid (TNBS) and were sacrificed 1, 2, 3, 4, 6, 12 and
24h later. Coronal frozen sections of the brain were cut and mRNAs encoding the rat c-fos, CRF1
receptor, CRF2
,
receptors were assayed by in situ hybridisation histochemistry. Localization of
these transcripts within CRF-immunoreactive (ir) neurons of the paraventricular nucleus (PVN) of
the hypothalamus was also determined. Intracolonic TNBS induced c-fos mRNA expression in
brain nuclei involved in the autonomic, behavioural and neuroendocrine response to a stimulus
(PVN, amygdala, locus coeruleus, parabrachial nucleus, nucleus tractus solitarius) and in
circumventricular organs (lamina terminalis, subfornical organ, area postrema). CRF pathways, in
particular in the PVN, were activated in this model as represented by a robust signal of c-fos and
CRF1 receptor transcripts in the PVN and numerous CRF-ir neurons expressed c-fos or CRF1
receptor transcripts in the PVN of TNBS-treated animals. No expression of CRF2 receptor
transcripts was observed in the PVN either in basal conditions or after TNBS. These
neuroanatomical data argue for an involvement of CRF pathways, through CRF1 receptor, within
the PVN in TNBS-induced colitis.
