What is the cellular source of prostaglandins in the brain in response to systemic inflammation? Facts and controversies

Rivest, Serge

doi:10.1038/sj.mp.4000676

Cited by 54 publications

(43 citation statements)

References 30 publications

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“…We and others have reported COX-2 mRNA expression exclusively within the cerebral endothelium in models of LPS, IL-1b or sterile systemic inflammation. 4,[11][12][13][14][15][16][17]20,21,23 In addition, colocalization of both mPGES-1 and COX-2 enzymes within brain endothelial cells was also observed, 18,36 and such results have yet to be reported in perivascular cells. Finally, COX-2 induction was localized to both endothelial and perivascular microglia in response to low doses of i.p.…”

Section: Discussionmentioning

confidence: 94%

“…11,37-40 COX inhibition prevents activation of PVN neurons and its afferent pathways in response to proinflammatory cytokines and LPS, 41,42 while intracerebral administration of PGE 2 stimulates these neuronal circuits and plasma ACTH and corticosterone release. [43][44][45] Moreover, both COX-2 and mPGES-1 are rapidly upregulated by circulating immune ligands 4,5,14,15,20,22,23,46 and COX-2-and mPGES-1-deficient mice do not develop fever in response to circulating LPS. 19,47,48 These mice do respond however to centrally administered PGE 2 .…”

Section: Discussionmentioning

confidence: 99%

“…10 Although COX-2 and mPGES-1 transcriptional activation takes place in cells of the BBB in various models of systemic inflammation, 4,11 the main cell type expressing these transcripts and producing PGE 2 is still under debate. Indeed, whereas numerous studies have provided evidence that both COX-2 and mPGES-1 transcripts and proteins are upregulated within the endothelium of the cerebral capillaries and venules, [12][13][14][15][16][17][18][19][20][21][22][23] other well-performed studies have shown that perivascular cells of hematopoietic origins play a key role in PGE 2 delivery in response to systemic inflammatory stimuli. [24][25][26] Finally, recent findings suggest that stimulation of both types of cells is required to activate the HPA axis during endotoxemia 27 and either types could mediate different phases of CNS activation.…”

Section: Introductionmentioning

confidence: 99%

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MyD88 signaling in brain endothelial cells is essential for the neuronal activity and glucocorticoid release during systemic inflammation

Gosselin

Rivest

2008

Mol Psychiatry

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Activation of neuronal circuits involved in the control of autonomic responses is critical for the host survival to immune threats. The brain vascular system plays a key role in such immune-CNS communication, but the signaling pathway and exact type of cells within the blood-brain barrier (BBB) mediating these functions have yet to be uncovered. To elucidate this issue we used myeloid differentiation factor 88 (MyD88)-deficient mice, because these animals do not show any responses to the cytokine interleukin-1b (IL-1b). We created chimeric mice with competent MyD88 signaling in either the BBB endothelium or perivascular microglia of bone marrow origin and challenged them with IL-1b. Systemic treatment with the cytokine caused a robust transcriptional activation of genes involved in the prostaglandin E 2 (PGE 2 ) production by vascular cells of the brain. Upregulation of these genes is dependent on a functional MyD88 signaling in the endothelium, because MyD88-deficient mice that received bone marrow stem cells from wild-type animals (for example, functional perivascular microglia) exhibited no response to systemic IL-1b administration. MyD88 competent endothelial cells also mediate neuronal activation and plasma release of glucocorticoids, whereas chimeric mice with MyD88-competent perivascular microglia did not show a significant increase of these functions. Moreover, competent endothelial cells for the gene encoding Toll-like receptor 4 (TLR4) are essential for the release of plasma corticosterone in response to low and high doses of lipopolysaccharide. Therefore, BBB endothelial cells and not perivascular microglia are the main target of circulating inflammatory mediators to activate the brain circuits and key autonomic functions during systemic immune challenges.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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MyD88 signaling in brain endothelial cells is essential for the neuronal activity and glucocorticoid release during systemic inflammation

Gosselin

Rivest

2008

Mol Psychiatry

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“…In the brain, prostaglandins are necessary mediators of some actions of proinflammatory cytokines (Rivest, 1999), including a subset (Avitsur, Weidenfeld, & Yirmiya, 1999;Dunn & Swiergiel, 2000;Johnson, Curtis, Dantzer, & Kelley, 1993;Yirmiya, Barak, Avitsur, Gallily, & Weidenfeld, 1997), though not all (Deak, D'Agonstino, Bellamy, Rosanoff, McElderry, & Bordner, 2005) behavioral components of sickness. Thus, the effect of indomethacin in Experiment 2 indicates a contribution of prostaglandins to the passive behaviors of guinea pig pups.…”

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory agents attenuate the passive responses of guinea pig pups: Evidence for stress-induced sickness behavior during maternal separation

Hennessy

Schiml-Webb

Miller

et al. 2007

Psychoneuroendocrinology

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A previous study found that intracerebroventricular (ICV) infusion of 25 μg of α-MSH reduced the passive responses (crouched stance, eye-closing, piloerection) of guinea pig pups during a 3-hr isolation in a novel environment. Because α-MSH has broad anti-inflammatory properties, the results suggested that proinflammatory factors play a role in mediating the behavior of isolated infants. The present study further investigated this possibility. In Experiment 1, injection of lipopolysacchride (LPS) increased the number of 60-s intervals in which pups expressed the same three responses during a 1-hr test, and ICV infusion of α-MSH significantly reduced the effect of LPS on crouching and piloerection. In Experiment 2, the prostaglandin synthesis inhibitor indomethacin (10mg/kg) reduced the number of 60-s intervals in which pups exhibited both crouching and the full suite of passive responses during a 3-hr isolation in a novel environment. Together these results provide further support for the hypothesis that the passive behaviors exhibited during prolonged isolation are "stressinduced sickness behaviors" mediated by proinflammatory factors. Keywords sickness behaviors; acute phase response; inflammation; maternal separation; isolation; guinea pig Stimulation of the innate immune system results in a systemic physiological and behavioral reaction known as the acute phase response or sickness (Baumann & Gauldie, 1994). Components of the acute phase response include: fever, shifts in the synthesis of liver proteins, activation of the hypothalamic-pituitary-adrenal system, sleepiness, assumption of a curled or hunched posture, piloerection, shivering, and reductions in various activities. Though the behavioral components may appear to be simply the result of debilitation, they are adaptive responses that contribute to recuperation by, for instance, supporting the production of fever (e.g., hunched posture, piloerection, shivering), which in turn, can inhibit further proliferation of pathogens (Aubert, 1999;Hart, 1988). The acute phase response is triggered by the release of proinflammatory cytokines (e.g., IL-1, IL-6, TNF-α) in the periphery and CNS (Dantzer, 2004).Address correspondence to: Michael B. Hennessy, PhD, Department of Psychology, 335 Fawcett Hall, Wright State University, 3640 Col Glenn Hwy, Dayton, OH 45435, 937.775.2943 (voice), 937.775.3347 (FAX), michael.hennessy@wright.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. In the last decade, it has become apparent that aspects of the acute phase response, including sickness behaviors, do not occur solely ...

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“…[41][42][43] DHA inhibits NF-kB activity via a peroxisome proliferator activated receptor-dependent mechanism in human breast cancer cells. 44 DHA also inhibits nuclear translocation of NF-kB in Jurat T cells 45 and inactivates NF-kB p65 in CaCo-2 cells.…”

Section: Discussionmentioning

confidence: 99%

Dietary n-3 PUFA deprivation alters expression of enzymes of the arachidonic and docosahexaenoic acid cascades in rat frontal cortex

et al. 2006

Mol Psychiatry

178

150

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The enzymes that regulate the brain arachidonic acid (AA) cascade have been implicated in bipolar disorder and neuroinflammation. Fifteen weeks of dietary n-3 polyunsaturated fatty acid (PUFA) deprivation in rats decreases the concentration of docosahexaenoic acid (DHA) and increases its half-life within the brain. Based on this, we hypothesized that such dietary deprivation would decrease expression of enzymes responsible for the metabolic loss of DHA while increasing expression of those responsible for the metabolism of AA. Fifteen weeks of n-3 PUFA deprivation significantly decreased the activity, protein and mRNA expression of the DHA regulatory phospholipase A 2 (PLA 2 ), calcium-independent iPLA 2 , in rat frontal cortex. In contrast the activities, protein and mRNA levels of the AA selective calcium-dependent cytosolic phospholipase (cPLA 2 ) and secretory sPLA 2 were increased. Cyclooxygenase (COX)-1 protein but not mRNA was decreased in the n-3 PUFA-deprived rats whereas COX-2 protein and mRNA were increased. This study suggests that n-3 PUFA deprivation increases the halflive of brain DHA by downregulating iPLA 2 . The finding that n-3 PUFA deprivation increases cPLA 2 , sPLA 2 and COX-2 is opposite to what has been reported after chronic administration of anti-manic agents to rats and suggests that n-3 PUFA deprivation may increase susceptibility to bipolar disorder. Molecular Psychiatry (2007) 12, 151-157.

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What is the cellular source of prostaglandins in the brain in response to systemic inflammation? Facts and controversies

Cited by 54 publications

References 30 publications

MyD88 signaling in brain endothelial cells is essential for the neuronal activity and glucocorticoid release during systemic inflammation

MyD88 signaling in brain endothelial cells is essential for the neuronal activity and glucocorticoid release during systemic inflammation

Anti-inflammatory agents attenuate the passive responses of guinea pig pups: Evidence for stress-induced sickness behavior during maternal separation

Dietary n-3 PUFA deprivation alters expression of enzymes of the arachidonic and docosahexaenoic acid cascades in rat frontal cortex

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