Distribution and characterization of cyclooxygenase immunoreactivity in the ovine brain

Breder, Christopher D.; Smith, William L.; Raz, Amiram; Masferrer, Jamie; Seibert, Karen; Needleman, Phillip; Saper, Clifford B.

doi:10.1002/cne.903220309

Cited by 165 publications

(76 citation statements)

References 108 publications

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“…In accordance with the literature [43,[62][63][64], analysis of constitutive COX2 immunoreactivity in the brain of control animals revealed positive neurons in the hippocampus (dentate gyrus granule cells, pyramidal cell neurons), piriform superficial cell layers of neocortex, the amygdala and, at a very low number, in the striatum, thalamus and hypothalamus (electronic supplementary material, figures S2 and S3). There were no positive cells in the substantia nigra, globus pallidus, entopeduncular and subthalamic nuclei.…”

Section: Results (A) Behavioural Observations and Effect Of 7nisupporting

confidence: 88%

Are cyclooxygenase-2 and nitric oxide involved in the dyskinesia of Parkinson's disease induced byl-DOPA?

Bortolanza

Padovan-Neto

Cavalcanti-Kiwiatkoski

et al. 2015

Phil. Trans. R. Soc. B

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Inflammatory mechanisms are proposed to play a role in l -DOPA-induced dyskinesia. Cyclooxygenase-2 (COX2) contributes to inflammation pathways in the periphery and is constitutively expressed in the central nervous system. Considering that inhibition of nitric oxide (NO) formation attenuates l -DOPA-induced dyskinesia, this study aimed at investigating if a NO synthase (NOS) inhibitor would change COX2 brain expression in animals with l -DOPA-induced dyskinesia. To this aim, male Wistar rats received unilateral 6-hydroxydopamine microinjection into the medial forebrain bundle were treated daily with l -DOPA (21 days) combined with 7-nitroindazole or vehicle. All hemi-Parkinsonian rats receiving l -DOPA showed dyskinesia. They also presented increased neuronal COX2 immunoreactivity in the dopamine-depleted dorsal striatum that was directly correlated with dyskinesia severity. Striatal COX2 co-localized with choline-acetyltransferase, calbindin and DARPP-32 (dopamine-cAMP-regulated phosphoprotein-32), neuronal markers of GABAergic neurons. NOS inhibition prevented l -DOPA-induced dyskinesia and COX2 increased expression in the dorsal striatum. These results suggest that increased COX2 expression after l -DOPA long-term treatment in Parkinsonian-like rats could contribute to the development of dyskinesia.

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Section: Results (A) Behavioural Observations and Effect Of 7nisupporting

confidence: 88%

Are cyclooxygenase-2 and nitric oxide involved in the dyskinesia of Parkinson's disease induced byl-DOPA?

Bortolanza

Padovan-Neto

Cavalcanti-Kiwiatkoski

et al. 2015

Phil. Trans. R. Soc. B

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“…Our results differ from several in vivo studies that demonstrate that COX is expressed predominantly by neurons and is barely detectable in glia (Breder et al, 1992;Yamagata et al, 1993;Norton et al, 1996). The reason for the discrepancy between the in vitro and in vivo studies is not clear.…”

Section: Prostaglandin Synthesis By Cultured Astrocytes and Neuronscontrasting

confidence: 99%

Transforming Growth Factor β1 Regulates the Expression of Cyclooxygenase in Cultured Cortical Astrocytes and Neurons

Luo¹,

Lang²,

Miller

1998

Journal of Neurochemistry

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Abstract:The hypothesis that transforming growth factor ßl (TGFß1) regulates the synthesis of prostaglandins by CNS tissue was tested by using purified cultures of cortical astrocytes or neurons that were obtained from rat pups on postnatal day 4 or 5 or fetuses on gestational day 16, respectively. The cells were exposed to TGFß1 for 2 days. The synthesis of prostaglandins depends upon the production and conversion of arachidonic acid, steps that are catalyzed by phospholipase A 2 (PLA2) and cyclooxygenase (COX), respectively. Prostaglandin E2 (PGE2) concentration was determined by radioimmunoassay. The expression of cytosolic PLA2 and COX (the constitutive COX1 and the inducible COX2) was assessed by using immunohistochemical and quantitative immunoblotting procedures. Astrocytes produced much more PGE2 than neurons, suggesting that glial cells are an important source of PGE2 in the CNS. TGF/31 increased the production of PGE2 by astrocytes and neurons in a concentration-dependent manner. Furthermore, TGFß1 enhanced COX activity; the inhibitor indomethacin completely blocked TGF/31-mediated PGE2 synthesis. Cultured astrocytes and neurons expressed the three enzymes: cytosolic PLA2, COX1, and COX2. Cytosolic PLA2 expression was unaffected by TGFf31 treatment. In contrast, COX expression was altered by TGF~31treatment in a concentration-dependent fashion. COX1 was increased by TGFß1, but only in astrocytes. TGFß1 increased COX2 expression in astrocytes and neurons. Thus, TGFß1 -induced increases in PGE2 concentration are regulated by COX. This study suggests that TGF/31 is an important regulator of immune and inflammatory processes in the CNS. Key Words: Cell culture-Cerebral cortex-Cytokine-Phospholipase A2-Prostaglandin. J. Neurochem. 71, 526-534 (1998).Prostaglandins, thromboxanes, and prostacyclin, collectively called prostanoids, are metabolites of arachidonic acid (AA). The initial step of prostanoid synthesis, the production of AA from fatty acids, is catalyzed by phospholipases, primarily phospholipase A2 (PLA2). AA is then converted to a prostanoid by cyclooxygenase (COX). There are at least two isoforms of COX: the constitutive COX1 and the inducible COX2.Prostanoids are commonly known as pivotal regulators of immune and inflammatory processes (Plescia and Racis, 1988). They are also present in the CNS, where they play important roles in the regulation of diverse CNS functions, i.e., cerebral blood flow, the sleep/wake cycle, and temperature regulation (Wolfe, 1982;Rothwell, 1992; Hayaishi, 1994). Although prostanoid concentrations are low in brain under normal conditions, they are increased in pathological states, such as ischemia, seizures, multiple sclerosis, acquired immunodeficiency syndrome, alcohol intoxication, and inflammation (Chen et al., 1986;George et al., 1986;Shimizu and Wolfe, 1990;Fretland, 1992;Griffin et al., 1994).Various growth factors, e.g., transforming growth factor ß (TGFß), have functions that parallel those of the prostanoids. Three isoforms of TGFß (TGF/31, TGF/32, and TGFß3...

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“…COX2 has also been found in postmortem human brain (reviewed by O'Banion, 1999). COX2 protein is normally found in neuronal cell bodies and dendrites (Tsubokura et al, 1991;Breder et al, 1992Breder et al, , 1995Kaufmann et al, 1996). Basal levels of COX2 are found in the neurons of the cortex and hippocampus, but not in glia or endothelial cells.…”

Section: Introductionmentioning

confidence: 99%

Prolonged Cyclooxygenase-2 Induction in Neurons and Glia Following Traumatic Brain Injury in the Rat

Strauss

Barbe

Marshall

et al. 2000

Journal of Neurotrauma

110

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Cyclooxygenase-2 (COX2) is a primary inflammatory mediator that converts arachidonic acid into precursors of vasoactive prostaglandins, producing reactive oxygen species in the process. Under normal conditions COX2 is not detectable, except at low abundance in the brain. This study demonstrates a distinctive pattern of COX2 increases in the brain over time following traumatic brain injury (TBI). Quantitative lysate ribonuclease protection assays indicate acute and sustained increases in COX2 mRNA in two rat models of TBI. In the lateral fluid percussion model, COX2 mRNA is significantly elevated (>twofold, p < 0.05, Dunnett) at 1 day postinjury in the injured cortex and bilaterally in the hippocampus, compared to sham-injured controls. In the lateral cortical impact model (LCI), COX2 mRNA peaks around 6 h postinjury in the ipsilateral cerebral cortex (fivefold induction, p < 0.05, Dunnett) and in the ipsilateral and contralateral hippocampus (two-and sixfold induction, respectively, p < 0.05, Dunnett). Increases are sustained out to 3 days postinjury in the injured cortex in both models. Further analyses use the LCI model to evaluate COX2 induction. Immunoblot analyses confirm increased levels of COX2 protein in the cortex and hippocampus. Profound increases in COX2 protein are observed in the cortex at 1-3 days, that return to sham levels by 7 days postinjury (p < 0.05, Dunnett). The cellular pattern of COX2 induction following TBI has been characterized using immunohistochemistry. COX2-immunoreactivity (-ir) rises acutely (cell numbers and intensity) and remains elevated for several days following TBI. Increases in COX2-ir colocalize with neurons (MAP2-ir) and glia (GFAP-ir). Increases in COX2-ir are observed in cerebral cortex and hippocampus, ipsilateral and contralateral to injury as early as 2 h postinjury. Neurons in the ipsilateral parietal, perirhinal and piriform cortex become intensely COX2-ir from 2 h to at least 3 days postinjury. In agreement with the mRNA and immunoblot results, COX2-ir appears greatest in the contralateral hippocampus. Hippocampal COX2-ir progresses from the pyramidal cell layer of the CA1 and CA2 region at 2 h, to the CA3 pyramidal cells and dentate polymorphic and granule cell layers by 24 h postinjury. These increases are distinct from those observed following inflammatory challenge, and correspond to brain areas previously identified with the neurological and cognitive deficits associated with TBI. While COX2 induction following TBI may result in selective beneficial responses, chronic COX2 production may contribute to free radical mediated cellular damage, vascular dysfunction, and alterations in cellular metabolism. These may cause secondary injuries to the brain that promote neuropathology and worsen behavioral outcome.

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Distribution and characterization of cyclooxygenase immunoreactivity in the ovine brain

Cited by 165 publications

References 108 publications

Are cyclooxygenase-2 and nitric oxide involved in the dyskinesia of Parkinson's disease induced byl-DOPA?

Are cyclooxygenase-2 and nitric oxide involved in the dyskinesia of Parkinson's disease induced byl-DOPA?

Transforming Growth Factor β1 Regulates the Expression of Cyclooxygenase in Cultured Cortical Astrocytes and Neurons

Prolonged Cyclooxygenase-2 Induction in Neurons and Glia Following Traumatic Brain Injury in the Rat

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