Neuronal activity and CRF receptor gene transcription in the brains of rats with colitis.

Abstract

We aimed to characterize neuronal and corticotropin-releasing factor (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 killed 1, 2, 3, 4, 6, 12, or 24 h later. Coronal frozen sections of the brain were cut and mRNAs encoding the rat c-fos, CRF1 receptor, and CRF2alpha,beta receptors were assayed by in situ hybridization histochemistry. Localization of these transcripts within CRF-immunoreactive (CRF-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, behavioral, and neuroendocrine response to a stimulus (PVN, amygdala, locus coeruleus, parabrachial nucleus, nucleus of the solitary tract) and in circumventricular organs (lamina terminalis, subfornical organ, area postrema). CRF pathways, particularly 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.