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| 2. |
- Engblom, David, 1975-, et al.
(författare)
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Activation of prostanoid EP3 and EP4 receptor mRNA-expressing neurons in the rat parabrachial nucleus by intravenous injection of bacterial wall lipopolysaccharide
- 2001
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Ingår i: Journal of Comparative Neurology. - : Wiley. - 0021-9967 .- 1096-9861. ; 440:4, s. 378-386
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Tidskriftsartikel (refereegranskat)abstract
- 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 central prostaglandin-mediated mechanisms. Recently, we have shown that neurons in the parts of the parabrachial nucleus that are activated by immune challenge express prostaglandin receptors of the EP3 and EP4 subtypes, but it remains to be determined if the prostaglandin receptor-expressing neurons are identical to those that respond to immune stimuli. In the present study, bacterial wall lipopolysaccharide was injected intravenously in adult male rats and the expression of c-fos mRNA and of EP3 and EP4 receptor mRNA was examined with complementary RNA probes labeled with digoxigenin and radioisotopes, respectively. Large numbers of neurons in the external lateral parabrachial subnucleus, a major target of vagal-solitary tract efferents, expressed c-fos mRNA. Quantitative analysis showed that about 60% (range 40%–79%) of these neurons also expressed EP3 receptor mRNA. Conversely, slightly more than 50% (range 48%–63%) of the EP3 receptor-expressing neurons in the same subnucleus coexpressed c-fos mRNA. In contrast, few EP4 receptor-expressing neurons were c-fos positive, with the exception of a small population located in the superior lateral and dorsal lateral subnuclei. These findings show that immune challenge activates central autonomic neurons that could be the target of centrally produced prostaglandin E2, suggesting that synaptic signaling and paracrine mechanisms may interact on these neurons. J. Comp. Neurol. 440:378–386, 2001. © 2001 Wiley-Liss, Inc.
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| 3. |
- Engblom, David, et al.
(författare)
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Distribution of prostaglandin EP3 and EP4 receptor mRNA in the rat parabrachial nucleus
- 2000
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Ingår i: Neuroscience Letters. - : Elsevier Science B.V., Amsterdam.. - 0304-3940 .- 1872-7972. ; 281:2-3, s. 163-166
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Tidskriftsartikel (refereegranskat)abstract
- By using in situ hybridization, the distribution of mRNA for the PGE2 receptors EP3 and EP4 was examined in the rat parabrachial nucleus (PB), a major brain stem relay for autonomic and nociceptive processing. EP3 receptor mRNA was present in most subnuclei, with the densest labeling in the external lateral, dorsal lateral, superior lateral, central lateral and Kölliker–Fuse nuclei. EP4 receptor mRNA expressing cells had a more restricted distribution, largely being confined to the superior lateral and adjacent parts of the dorsal and central lateral nuclei in a pattern complementary to that for EP3 receptor mRNA. These findings suggest that EP3 and EP4 receptors in PB have distinct functional roles that include nociceptive processing, blood pressure regulation and feeding behavior.
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| 4. |
- Engblom, David, 1975-, et al.
(författare)
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EP3 and EP4 receptor mRNA expression in peptidergic cell groups of the rat parabrachial nucleus
- 2004
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Ingår i: Neuroscience. - : Elsevier BV. - 0306-4522 .- 1873-7544. ; 126:4, s. 989-999
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Tidskriftsartikel (refereegranskat)abstract
- This study examines the distribution of prostaglandin E2 receptors of subtype EP3 and EP4 among brain stem parabrachial neurons that were characterized with respect to their neuropeptide expression. By using a dual-labeling in situ hybridization method, we show that preprodynorphin mRNA expressing neurons in the dorsal and central lateral subnuclei express EP3 receptor mRNA. Such receptors are also expressed in preproenkephalin, calcitonin gene related peptide and preprotachykinin mRNA positive neurons in the external lateral subnucleus, whereas preprodynorphin mRNA expressing neurons in this subnucleus are EP receptor negative. In addition, EP3 receptor expression is seen among some enkephalinergic neurons in the Kölliker-Fuse nucleus. Neurons in the central part of the cholecystokininergic population in the regions of the superior lateral subnucleus express EP4 receptor mRNA, whereas those located more peripherally express EP3 receptors. Taken together with previous findings showing that discrete peptidergic cell groups mediate nociceptive and/or visceral afferent information to distinct brain stem and forebrain regions, the present results suggest that the processing of this information in the parabrachial nucleus is influenced by prostaglandin E2. Recent work has shown that prostaglandin E2 is released into the brain following peripheral immune challenge; hence, the parabrachial nucleus may be a region where humoral signaling of peripheral inflammatory events may interact with neuronal signaling elicited by the same peripheral processes.
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- Engblom, David, 1975-, et al.
(författare)
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Induction of microsomal prostaglandin E synthase in the rat brain endothelium and parenchyma in adjuvant-induced arthritis
- 2002
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Ingår i: Journal of Comparative Neurology. - : Wiley. - 0021-9967 .- 1096-9861. ; 452:3, s. 205-214
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Tidskriftsartikel (refereegranskat)abstract
- Although central nervous symptoms such as hyperalgesia, fatigue, malaise, and anorexia constitute major problems in the treatment of patients suffering from chronic inflammatory disease, little has been known about the signaling mechanisms by which the brain is activated during such conditions. Here, in an animal model of rheumatoid arthritis, we show that microsomal prostaglandin E-synthase, the inducible terminal isomerase in the prostaglandin E2-synthesizing pathway, is expressed in endothelial cells along the blood-brain barrier and in the parenchyma of the paraventricular hypothalamic nucleus. The endothelial cells but not the paraventricular hypothalamic cells displayed a concomitant induction of cyclooxygenase-2 and expressed interleukin-1 type 1 receptors, which indicates that the induction is due to peripherally released cytokines. In contrast to cyclooxygenase-2, microsomal prostaglandin E synthase had very sparse constitutive expression, suggesting that it could be a target for developing drugs that will carry fewer side effects than the presently available cyclooxygenase inhibitors. These findings, thus, suggest that immune-to-brain communication during chronic inflammatory conditions involves prostaglandin E2-synthesis both along the blood-brain barrier and in the parenchyma of the hypothalamic paraventricular nucleus and point to novel avenues for the treatment of the brain-elicited disease symptoms during these conditions.
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| 6. |
- Engblom, David, 1975-, et al.
(författare)
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Prostaglandins as inflammatory messengers across the blood-brain barrier
- 2002
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Ingår i: Journal of Molecular Medicine. - : Springer Science and Business Media LLC. - 0946-2716 .- 1432-1440. ; 80:1
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Tidskriftsartikel (refereegranskat)abstract
- Upon immune challenge the brain launches a wide range of responses, such as fever, anorexia, and hyperalgesia that serve to maintain homeostasis. While these responses are adaptive during acute infections, they may be destructive during chronic inflammatory conditions. Research performed during the last decade has given us insight into how the brain monitors the presence of a peripheral inflammation and the mechanisms underlying the brain-mediated acute-phase reactions. Here we give a brief review on this subject, with focus on the role of prostaglandin E2 produced in cells associated with the blood-brain barrier in immune-to-brain signaling. The recent advances in this field have not only elucidated the mechanisms behind the anti-pyretic and anti-hyperalgesic effects of cyclooxygenase inhibitors, but have also identified novel and more-selective potential drug targets.
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