Neuron
Volume 11, Issue 2, August 1993, Pages 371-386
Journal home page for Neuron

Article
Expression of a mitogen-inducible cyclooxygenase in brain neurons: Regulation by synaptic activity and glucocorticoids

https://doi.org/10.1016/0896-6273(93)90192-TGet rights and content

Abstract

Prostaglandins play important and diverse roles in the CNS. The first step in prostaglandin synthesis involves enzymatic oxidation of arachidonic acid, which is catalyzed by prostaglandin H(PGH) synthase, also referred to as cyclooxygenase. We have cloned an inducible form of this enzyme from rat brain that is nearly identical to a murine, mitogen-inducible cyclooxygenase identified from fibroblasts. Our studies indicate that this gene, here termed COX-2, is expressed throughout the forebrain in discrete populations of neurons and is enriched in the cortex and hippocampus. Neuronal expression is rapidly and transiently induced by seizures or NMDA-dependent synaptic activity. No expression is detected in glia or vascular endothelial cells. Basal expression of COX-2 appears to be regulated by natural synaptic activity in the developing and adult brain. Both basal and induced expression of COX-2 are inhibited by glucocorticoids, consistent with COX-2 regulation in peripheral tissues. Our studies indicate that COX-2 expression may be important in regulating prostaglandin signaling in brain. The marked inducibility in neurons by synaptic stimuli suggests a role in activity-dependent plasticity.

References (90)

  • D.A. Kujubu et al.

    Dexamethasone inhibits mitogen induction of the TIS10 prostaglandin synthase cyclooxygenase gene

    J. Biol. Chem.

    (1992)
  • D.A. Kujubu et al.

    TIS10, a phorbol ester tumor promoter-inducible mRNA from Swiss 3T3 cells, encodes a novel prostaglandin synthase/cyclooxygenase homologue

    J. Biol. Chem.

    (1991)
  • D.A. Kujubu et al.

    Expression of the protein product of the prostaglandin synthase-2/TIS10 gene in mitogen-stimulated Swiss 3T3 cells

    J. Biol. Chem.

    (1993)
  • S.H. Lee et al.

    Selective expression of mitogen-inducible cyclooxygenase in macrophages stimulated with lipopolysaccharide

    J. Biol. Chem.

    (1992)
  • M.A. Lynch et al.

    Nordihydroguaiaretic acid blocks the synaptic component of long-term potentiation and the associated increases in release of glutamate and arachidonate: an in vivo study in the dentate gyrus of the rat

    Neuroscience

    (1989)
  • C.M. Markey et al.

    Quantitative studies of hydroperoxide reduction by prostaglandin H synthase. Reducing substrate specificity and the relationship of peroxidase to cyclooxygenase activities

    J. Biol. Chem.

    (1987)
  • P.J. Marshall et al.

    Constraints of prostaglandin biosynthesis in tissues

    J. Biol. Chem.

    (1987)
  • E.A. Meade et al.

    Differential inhibition of prostaglandin endoperoxide synthase (cyclooxygenase) isozymes by aspirin and other non-steroidal anti-inflammatory drugs

    J. Biol. Chem.

    (1993)
  • J.P. Merlie et al.

    Isolation and characterization of the complementary DNA for sheep seminal vesicle prostaglandin endoperoxidase synthase (cyclooxygenase)

    J. Biol. Chem.

    (1988)
  • S. Narumiya et al.

    Prostaglandin D2 in rat brain, spinal cord and pituitary: basal level and regional distribution

    Life Sci.

    (1982)
  • R.A. Nicoll et al.

    The current excitement in long-term potentiation

    Neuron

    (1988)
  • M. O'Sullivan et al.

    Lipopolysaccharide priming of alveolar macrophages for enhanced synthesis of prostanoids involves induction of a novel prostaglandin H synthase

    J. Biol. Chem.

    (1992)
  • A. Raz et al.

    Regulation of fibroblast cyclooxygenase synthesis by interleukin-1

    J. Biol. Chem.

    (1988)
  • C.J. Shatz

    Impulse activity and the patterning of connections during CNS development

    Neuron

    (1990)
  • G. Shaw et al.

    A conserved sequence from the 3′-untranslated region of GM-CSF mRNA mediates selective mRNA degradation

    Cell

    (1986)
  • M. Sheng et al.

    The regulation and function of c-fos and other immediate early genes in the nervous system

    Neuron

    (1990)
  • J. Sirois et al.

    Hormonal regulation of messenger ribonucleic acid encoding a novel isoform of prostaglandin endoperoxide H synthase in rat preovulatory follicles

    J. Biol. Chem.

    (1992)
  • W.L. Smith et al.

    Prostaglandin and thromboxane biosynthesis

    Pharmacol. Ther.

    (1991)
  • E.A. Stone et al.

    Effect of locus coeruleus lesion on c-fos expression in the cerebral cortex caused by yohimbine injection or stress

    Brain Res.

    (1993)
  • S. Tsubokura et al.

    Localization of prostaglandin endoperoxide synthase in neurons and glia in monkey brain

    Brain Res.

    (1991)
  • A.M. Turner et al.

    Differential rearing effects on rat visual cortex synapses. I. Synaptic and neuronal density and synapses per neuron

    Brain Res.

    (1985)
  • Y. Urade et al.

    Postnatal changes in the localization of prostaglandin D synthetase from neurons to oligodendrocytes in the rat brain

    J. Biol. Chem.

    (1987)
  • Y. Watanabe et al.

    Modulation by prostaglandin D2 of mitral cell responses to odor stimulation in rabbit olfactory bulb

    Brain Res.

    (1986)
  • C. Yokoyama et al.

    Cloning of human gene encoding prostaglandin endoperoxide synthase and primary structure of the enzyme

    Biochem. Biophys. Res. Commun.

    (1989)
  • C. Yokoyama et al.

    Primary structure of sheep prostaglandin endoperoxidase synthase deduced from cDNA sequence

    FEBS Lett.

    (1988)
  • W.C. Abraham et al.

    The role of immediate early genes in the stabilization of long-term potentiation

    Mol. Neurobiol.

    (1992)
  • C.A. Barnes et al.

    An age comparison of the rates of acquisition and forgetting of spatial information in relation to long-term enhancement of hippocampal synapses

    Behav. Neurosci.

    (1985)
  • T.V.P. Bliss et al.

    A synaptic model of memory: long-term potentiation in the hippocampus

    Nature

    (1993)
  • M.E. Blue et al.

    The formation and maturation of synapses in the visual cortex of the rat. II. Quantitative analysis

    J. Neurocytol.

    (1983)
  • C.D. Breder et al.

    Distribution and characterization of cyclooxygenase immunoreactivity in the ovine brain

    J. Comp. Neurol.

    (1992)
  • W.B. Campbell

    Lipid-derived autacoids: eicosanoids and platelet-activating factor

  • G. Carmignoto et al.

    Activity-dependent decrease in NMDA receptor responses during development of the visual cortex

    Science

    (1992)
  • S. Ceccatelli et al.

    Expression of c-Fos immunoreactivity in transmitter-characterized neurons after stress

  • A.J. Cole et al.

    Rapid rise in transcription factor messenger RNAs in rat brain after electroshock induced seizures

    J. Neurochem.

    (1990)
  • T.M. Dawson et al.

    Nitric oxide synthase and neuronal NADPH diaphorase are identical in brain and peripheral tissues

  • Cited by (0)

    View full text