David Engblom, Monica Ek, Ingela M Andersson, Sipra Saha, Marie Dahlström, Per-Johan Jakobsson, Anders Ericsson-Dahlstrand, Anders Blomqvist
The Journal of Comparative Neurology, 2002, Oct 21; 452(3)205
DOI: https://doi.org/10.1002/cne.10380
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.
The induction of microsomal prostaglandin E synthase (mPGES) in both the brain endothelium and parenchyma of rats with adjuvant-induced arthritis sheds light on the intricate mechanisms underlying inflammatory responses. Understanding how mPGES is upregulated in these specific regions enhances our comprehension of the neuroinflammatory processes associated with arthritis. This finding not only underscores the complexity of the brain's involvement in peripheral inflammatory conditions but also underscores the potential role of mPGES as a therapeutic target. For further exploration of this fascinating link between brain inflammation and arthritis, researchers may benefit from delving deeper into the molecular pathways affected. You can click this link now for more insights into mPGES regulation, and click this over here now to explore potential therapeutic interventions.