Hippocampal upregulation of the cyclooxygenase-2 gene following neonatal clomipramine treatment (a model of depression)

Cassano, Paola; Hidalgo, Alejandra; Burgos, Valeria; Adris, Soraya; Argibay, Pablo

doi:10.1038/sj.tpj.6500385

Cited by 40 publications

(22 citation statements)

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“…Neonatal clomipramine administration resulted in decreased BDNF levels in the hippocampus (Cassano et al 2006) and also resulted in deficits of cellular signal transduction in the frontal cortex and hippocampus indicated by a large decrease of phosphorylated extracellular signal-regulated kinase (ERK) (Feng et al 2003). Musazzi et al (2010) have recently reported that early life stress and antidepressant treatment involve synaptic dysfunction and alterations of ERK as well as CaM kinase/NMDA in the hippocampus.…”

Section: Discussionmentioning

confidence: 99%

“…Further, firing frequency was attenuated in the dorsal raphe nucleus, and serotonin, norepinephrine, and dopamine levels were decreased in the hippocampus, frontal cortex, brainstem, septum, and hypothalamus (Vijayakumar and Meti 1999;Yavari et al 1993). Neonatal clomipramine exposure resulted in reduced cortical and medullary weight, total protein, and DNA (Mirmiran et al 1983); decreased levels of the brain-derived neurotrophic factor in the hippocampus (Cassano et al 2006); and deficits of cellular signal transduction in the frontal cortex and hippocampus indicated by a large decrease of phosphorylated extracellular signal-regulated kinase (Feng et al 2003).…”

Section: Introductionmentioning

confidence: 99%

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Chronic escitalopram treatment restores spatial learning, monoamine levels, and hippocampal long-term potentiation in an animal model of depression

et al. 2010

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Chronic escitalopram treatment restores spatial learning, monoamine levels, and hippocampal long-term potentiation in an animal model of depression

et al. 2010

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“…In an other animal model of depression, an increased expression of COX-2 in the hippocampus was observed; preliminary data from this group point to an antidepressant effect of COX-2 inhibitors in this model. 209 A possible mechanism of the antidepressant action of COX-2 inhibitors is the inhibition of the release of IL-1 and IL-6. Moreover, COX-2 inhibitors also protect the CNS from effects of quinolinic acid.…”

Section: Antidepressant Pharmacotherapymentioning

confidence: 99%

The immune-mediated alteration of serotonin and glutamate: towards an integrated view of depression

2007

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Beside the well-known deficiency in serotonergic neurotransmission as pathophysiological correlate of major depression (MD), recent evidence points to a pivotal role of increased glutamate receptor activation as well. However, cause and interaction of these neurotransmitter alterations are not understood. In this review, we present a hypothesis integrating current concepts of neurotransmission and hypothalamus-pituitary-adrenal (HPA) axis dysregulation with findings on immunological alterations and alterations in brain morphology in MD. An immune activation including increased production of proinflammatory cytokines has repeatedly been described in MD. Proinflammatory cytokines such as interleukin-2, interferon-c, or tumor necrosis factor-a activate the tryptophan-and serotonin-degrading enzyme indoleamine 2,3-dioxygenase (IDO). Depressive states during inflammatory somatic disorders are also associated with increased proinflammatory cytokines and increased consumption of tryptophan via activation of IDO. An enhanced consumption of serotonin and its precursor tryptophan through IDO activation could well explain the reduced availability of serotonergic neurotransmission in MD. An increased activation of IDO and its subsequent enzyme kynurenine monooxygenase by proinflammatory cytokines, moreover, leads to an enhanced production of quinolinic acid, a strong agonist of the glutamatergic N-methyl-D-aspartate receptor. In inflammatory states of the central nervous system, IDO is mainly activated in microglial cells, which preferentially metabolize tryptophan to the NMDA receptor agonist quinolinic acid, whereas astrocytes -counteracting this metabolism due to the lack of an enzyme of this metabolism -have been observed to be reduced in MD. Therefore the type 1/type 2 immune response imbalance, associated with an astrocyte/microglia imbalance, leads to serotonergic deficiency and glutamatergic overproduction. Astrocytes are further strongly involved in re-uptake and metabolic conversion of glutamate. The reduced number of astrocytes could contribute to both, a diminished counterregulation of IDO activity in microglia and an altered glutamatergic neurotransmission. Further search for antidepressant agents should take into account anti-inflammatory drugs, for example, cyclooxygenase-2 inhibitors, might exert antidepressant effects by acting on serotonergic deficiency, glutamatergic hyperfunction and antagonizing neurotoxic effects of quinolinic acid. Molecular Psychiatry (2007) 12, 988-1000; doi:10.1038/sj.mp.4002006; published online 24 April 2007 Keywords: major depression; psychoneuroimmunology; IDO; glutamate; immune system; serotonin Glutamate in depressionGlutamatergic neurotransmission is involved in depression and interacts with the serotonergic and noradrenergic systems The common therapeutic mechanism of antidepressant drugs is the enhancement of serotonergic and/or noradrenergic neurotransmission. On the basis of this pharmacological profile of antidepressant drugs, neurochemical research on major depression ...

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“…If similar action occurs in the brain, 5-LOX inhibition could lead to antidepressant effects by preventing COX-2 upregulation. Namely, hippocampal COX-2 is upregulated in a rat model of depression [1] and a COX-2 inhibitor, celecoxib, demonstrated therapeutic effects in major depression [24].…”

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confidence: 99%

Effects of MK-886, a 5-lipoxygenase activating protein (FLAP) inhibitor, and 5-lipoxygenase deficiency on the forced swimming behavior of mice

Dimitrijević

Imbesi

et al. 2008

Neuroscience Letters

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A common biological pathway may contribute to the comorbidity of atherosclerosis and depression. Increased activity of the enzymatic 5-lipoxygenase (5-LOX; 5LO) pathway is a contributing factor in atherosclerosis and a 5-LOX inhibitor, MK-886, is beneficial in animal models of atherosclerosis. In the brain, MK-886 increases phosphorylation of the glutamate receptor subunit GluR1, and the increased phosphorylation of this receptor has been associated with antidepressant treatment. In this work, we evaluated the behavioral effects of MK-886 in an automated assay of mouse forced swimming, which identifies antidepressant activity as increased climbing behavior and/or decreased rest time. Whereas a single injection of MK-886 (3 and 10 mg/kg) did not affect forced swimming behaviors assayed 30 min later, 6 daily injections of 3 mg/kg MK-886 slightly increased climbing and significantly reduced rest time in wild-type mice but not in 5-LOX-deficient mice. A diet delivery of MK-886, 4 μg per 100 mg body-weight per day, required three weeks to affect forced swimming; it increased climbing behavior. Climbing behavior was also increased in naive 5-LOX-deficient mice compared to naive wild-type controls. These results suggest that 5-LOX inhibition and deficiency may be associated with antidepressant activity. Increased climbing in a forced swimming assay is a typical outcome of antidepressants that increase noradrenergic and dopaminergic activity. Interestingly, 5-LOX deficiency and MK-886 treatment have been shown to be capable of increasing the behavioral effects of a noradrenaline/dopamine-potentiating drug, cocaine. Future research is needed to evaluate the clinical relevance of our findings.Keywords 5-lipoxygenase (5-LOX, 5LO); antidepressant; depression; atherosclerosis; GluR1 cardiovascular Recent studies pointed out an association between depressive symptoms and the progression of atherosclerosis [7,26]. It was proposed that a common biological mechanism contributes to triggering and/or maintenance of these two pathological conditions [19].A prominent role in the pathobiology of atherosclerosis is played by 5-lipoxygenase (5-LOX; 5LO), an enzyme involved in the metabolism of arachidonic acid in 5(S)-hydroperoxy-6-trans-8,11,14-cis-eicosatetraenoic acid (5-HPETE) and leukotrienes [16,25]. Whereas an Correspondence: Radmila Manev, MD, Department of Psychiatry, Heart and Mind Clinic, University of Illinois at Chicago, 1601 West Taylor Street, MC912, Chicago, IL 60612, USA, e-mail: Rmanev@psych.uic.edu; phone: 312-413-3970; fax: 312-413-4569. 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...

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Hippocampal upregulation of the cyclooxygenase-2 gene following neonatal clomipramine treatment (a model of depression)

Cited by 40 publications

References 46 publications

Chronic escitalopram treatment restores spatial learning, monoamine levels, and hippocampal long-term potentiation in an animal model of depression

Chronic escitalopram treatment restores spatial learning, monoamine levels, and hippocampal long-term potentiation in an animal model of depression

The immune-mediated alteration of serotonin and glutamate: towards an integrated view of depression

Effects of MK-886, a 5-lipoxygenase activating protein (FLAP) inhibitor, and 5-lipoxygenase deficiency on the forced swimming behavior of mice

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