Activation of prostanoid EP3 and EP4 receptor mRNA-expressing neurons in the rat parabrachial nucleus by intravenous injection of bacterial wall lipopolysaccharide

Systemic inflammation activates central autonomic circuits, such as neurons in the pontine parabrachial nucleus. This activation may be the result of afferent signaling through the vagus nerve, but it may also depend on centr al prostaglandin-mediated mechanisms. Recently, we have shown that neurons in the parts of the parabrachial nucleus that are activated by immune chall enge express prostaglandin receptors of the EP3 and EP4 subtypes, but it re mains to be determined if the prostaglandin receptor-expressing neurons are identical to those that respond to immune stimuli. In the present study, b acterial wall lipopolysaccharide was injected intravenously in adult male r ats and the expression of c-fos mRNA and of EP3 and EP4 receptor mRNA was e xamined with complementary RNA probes labeled with digoxigenin and radioiso topes, respectively. Large numbers of neurons in the external lateral parab rachial subnucleus, a major target of vagal-solitary tract efferents, expre ssed c-fos mRNA. Quantitative analysis showed that about 60% (range 40%-79% ) of these neurons also expressed EP3 receptor mRNA. Conversely, slightly m ore than 50% (range 48%-63%) of the EP3 receptor-expressing neurons in the same subnucleus coexpressed c-fos m-RNA. In contrast, few EP4 receptor-expr essing neurons were c-fos positive, with the exception of a small populatio n located in the superior lateral and dorsal lateral subnuclei. These findi ngs show that immune challenge activates central autonomic neurons that cou ld be the target of centrally produced prostaglandin E-2, suggesting that s ynaptic signaling and paracrine mechanisms may interact on these neurons. ( C) 2001 Wiley-Liss, Inc.