title: Dissociation between c-fos mRNA in the paraventricular nucleus and corticosterone secretion in rats with adjuvant-induced arthritis.
abstract: Increased c-fos mRNA or fos immunoreactivity within the central nervous system has been used as a marker of neuronal activation. Acute stress and acute immune challenge result in an increase in c-fos mRNA in corticotrophin-releasing factor (CRF)-containing neurons in the paraventricular nucleus (PVN). It has often been implied that an increase in fos in the PVN can be equated to an increase in the activity of CRF itself, although there is some evidence to suggest these events are not linked. In the present study we have used the rat model of adjuvant-induced arthritis (AA), in which, despite the activation of the pituitary-adrenal system associated with inflammation, there is a paradoxical decrease in CRF mRNA and CRF peptide release. AA rats are unable to mount a hypothalamo-pituitary-adrenal (HPA) axis response to acute stress. They are, however, able to mount a response to acute immune stimulation, e.g. lipopolysaccharide injection. Despite the lack of HPA axis response to stress, there is an increase in c-fos mRNA to these challenges in AA. This suggests that the increase in c-fos mRNA in response to acute stress is not related to a subsequent increase in CRF mRNA in this model. We can conclude that under these conditions, c-fos mRNA is not a good marker of HPA axis activation and independent estimation of the involvement of CRF in the stimulation of the HPA axis should always be obtained. The AA model may prove useful for the comparison of the relationship between immediate early genes and heteronuclear RNAs in response to acute stress and immune stimuli with which to tease apart the molecular mechanisms underlying the control of releasing factor activation at the level of the PVN.
authors.affiliation: Division of Medicine, University of Bristol, Bristol Royal Infirmary, Marlborough Street, Bristol BS2 8HW, UK.
authors.forename: M S
authors.initials: MS
authors.lastname: Harbuz
authors.forename: D S
authors.initials: DS
authors.lastname: Jessop
mesh_terms: D000302:Adrenal Cortex / Q000503:physiopathology*; D000704:Analysis of Variance; D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism* / Q000503:physiopathology; D003345:Corticosterone / Q000097:blood / Q000378:metabolism*; D008070:Lipopolysaccharides; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D008070:Lipopolysaccharides; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D003345:Corticosterone