title: Bacterial endotoxin-induced gene expression in the choroid plexus and paraventricular and supraoptic hypothalamic nuclei of the sheep.
abstract: The febrile and neuroendocrine responses to circulating endotoxin are effected, at least in part, by a central action of prostaglandins with interleukins serving as intermediaries. Data from rodents suggest that prostaglandin and interleukin (IL-1 beta) synthesis in response to endotoxin challenge may occur within the circumventricular organs of the brain, especially the choroid plexus; the present study investigated this possibility using the sheep as an experimental model. A pyretic dose of bacterial endotoxin (40 micrograms lipopolysaccharide) was given intravenously to sheep (n = 5) and the effect on gene expression in the choroid plexus after a 40 min interval was compared with that observed in vehicle-treated animals (n = 5) using in situ hybridisation histochemistry. Evidence of activational and synthetic events following endotoxin administration was provided by significant increases in c-fos (P < 0.05) and IL-1 beta (P < 0.01) mRNA expression. Constitutive cyclooxygenase (cox-1 mRNA) and inducible cyclooxygenase (cox-2 mRNA) synthesis were unchanged. The investigation also sought to provide evidence for endotoxin effects on neuroendocrine activity in this species by examining changes in hypothalamic gene expression. The results showed that c-fos mRNA increased in the paraventricular (P < 0.01) and supraoptic (P < 0.05) nuclei and that CRH mRNA was upregulated in the paraventricular nucleus (P < 0.001). However, in agreement with previous work, there was no change in vasopressin gene expression although oxytocin mRNA was enhanced throughout the paraventricular nucleus (P < 0.05). These findings suggest the following: (1) possible involvement of the choroid plexus in the response of sheep to immunological challenge: (2) endotoxin-induced changes in gene expression in the ovine hypothalamus similar in those caused by other stressors: and (3) possible changes in oxytocin synthesis concomitant with fever in the sheep.
authors.affiliation: Department of Neurobiology, Babraham Institute, Cambridge, UK.
authors.forename: S V
authors.initials: SV
authors.lastname: Vellucci
authors.forename: R F
authors.initials: RF
authors.lastname: Parrott
mesh_terms: D000818:Animals; D002831:Choroid Plexus / Q000187:drug effects*; D004731:Endotoxins / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D007031:Hypothalamus / Q000187:drug effects*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects*; D012756:Sheep
chemical_list: D004731:Endotoxins