Maturational Regulation and Regional Induction of Cyclooxygenase-2 in Rat Brain: Implications for Alzheimer's Disease

Tocco, Georges; Freire-Moar, José; Schreiber, Sidney S.; Sakhi, Shahin; Aisen, Paul S.; Pasinetti, Giulio Maria

doi:10.1006/exnr.1997.6429

Cited by 163 publications

(100 citation statements)

References 43 publications

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“…These findings suggest that COX inhibitors could prevent seizure-induced neuronal damage by fully blocking PGE 2 synthesis (Takemya et al, 2006). In addition, another study showed that induction of COX expression paralleled formation of ROS indicating that COX may be involved in pathways leading to neuronal damage (Tocco et al, 1997). Since ibuprofen did not alter kainate seizure severity in our study, its neuroprotective effect is likely to be due to a decreased susceptibility of neurons to the effects of seizures.…”

Section: Discusionsupporting

confidence: 49%

Pharmacologic suppression of oxidative damage and dendritic degeneration following kainic acid-induced excitotoxicity in mouse cerebrum

et al. 2008

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Intense seizure activity associated with status epilepticus and excitatory amino acid (EAA) imbalance initiates oxidative damage and neuronal injury in CA1 of the ventral hippocampus. We tested the hypothesis that dendritic degeneration of pyramidal neurons in the CA1 hippocampal area resulting from seizure-induced neurotoxicity is modulated by cerebral oxidative damage. Kainic acid (KA, 1 nmol/5 μl) was injected intracerebroventricularly to C57Bl/6 mice. F 2 -isoprostanes (F 2 -IsoPs) and F 4 -neuroprostanes (F 4 -NeuroPs) were used as surrogate measures of in vivo oxidative stress and biomarkers of lipid peroxidation. Nitric oxide synthase (NOS) activity was quantified by evaluating citrulline level and pyramidal neuron dendrites and spines were evaluated using rapid Golgi stains and a Neurolucida system. KA produced severe seizures in mice immediately after its administration and a significant (p<0.001) increase in F 2 -IsoPs, F 4 -NeuroPs and citrulline levels were seen 30 min following treatment. At the same time, hippocampal pyramidal neurons showed significant (p<0.001) reduction in dendritic length and spine density. In contrast, no significant change in neuronal dendrite and spine density or F 2 -IsoP, F 4 -NeuroPs and citrulline levels were found in mice pretreated with Vitamin E (α-tocopherol, 100 mg/kg, ip) for 3 days, or with N-tert-butyl-α-phenylnitrone (PBN, 200 mg/kg, ip) or ibuprofen (inhibitors of cyclooxygenase, COX, 14 μg/ml of drinking water) for 2 weeks prior to KA treatment. These findings indicate novel interactions among free radical-induced generation of F 2 -IsoPs and F 4 -NeuroPs, nitric oxide and dendritic degeneration, closely associate oxidative damage to neuronal membranes with degeneration of the dendritic system, and point to possible interventions to limit severe damage in acute neurological disorders.

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Section: Discusionsupporting

confidence: 49%

Pharmacologic suppression of oxidative damage and dendritic degeneration following kainic acid-induced excitotoxicity in mouse cerebrum

et al. 2008

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“…11 In rodents, the response to kainic acid (KA)-mediated excitotoxicity, which may be a model for aspects of the hippocampal and cortical neurodegeneration observed in AD, includes a marked up-regulation of COX-2, although COX-1 remains unaffected. 12 The induction of COX-2 expression parallels the appearance of neuronal apoptotic features in cell types affected by KA, and excitotoxic neuronal death in vitro is accompanied by a selective elevation in COX-2 mRNA, indicating that COX-2 may be involved in pathways leading to neuronal death. 12 This information may have important implications for AD in view of the evidence that excitotoxicity may contribute to the widespread pattern of neurodegeneration in the AD brain.…”

mentioning

confidence: 93%

“…12 The induction of COX-2 expression parallels the appearance of neuronal apoptotic features in cell types affected by KA, and excitotoxic neuronal death in vitro is accompanied by a selective elevation in COX-2 mRNA, indicating that COX-2 may be involved in pathways leading to neuronal death. 12 This information may have important implications for AD in view of the evidence that excitotoxicity may contribute to the widespread pattern of neurodegeneration in the AD brain. 13 Recently we 14 and others 15 found elevation of expression of COX-2, but not COX-1, in neurons of the AD brain.…”

mentioning

confidence: 93%

Potentiation of Excitotoxicity in Transgenic Mice Overexpressing Neuronal Cyclooxygenase-2

Kelley

Winger

et al. 1999

The American Journal of Pathology

210

133

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In this study we describe the generation of a transgenic mouse model with neuronal overexpression of the human cyclooxygenase-2 , h(COX)-2 , to explore its role in excitotoxicity. We report that overexpression of neuronal hCOX-2 potentiates the intensity and lethality of kainic acid excitotoxicity in coincidence with potentiation of expression of the immediate early genes c-fos and zif-268. In vitro studies extended the in vivo findings and revealed that glutamate excitotoxicity is potentiated in primary cortico-hippocampal neurons derived from hCOX-2 transgenic mice , possibly through potentiation of mitochondrial impairment. This study is the first to demonstrate a cause-effect relationship between neuronal COX-2 expression and excitotoxicity. This model system will allow the systematic examination of the role of COX-2 in mechanisms of neurodegeneration that involve excitatory amino acid pathways. (Am J Pathol 1999, 155:995-1004) Cyclooxygenase (COX) is the rate-limiting enzyme in the production of prostaglandins and, as such, a key target for anti-inflammatory drugs. Indeed, aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are COX inhibitors.

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“…It has been found that multiple stimuli, including cytokines, hormones, ischemia, hypoxemia, epilepsy and phorbol ester can increase the expression of COX-2 (26). In the majority of cells, COX-2 expression can increase rapidly after an attack of epilepsy or cerebral ischemia and can be inhibited by corticosteroids (27).…”

Section: Discussionmentioning

confidence: 99%

Geniposide attenuates epilepsy symptoms in a mouse model through the PI3K/Akt/GSK‑3β signaling pathway

Wei¹,

Duan²,

He³

et al. 2017

Exp Ther Med

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Abstract. Previous reports on the pharmacological actions of geniposide have indicated that it has anti-asthmatic, anti-inflammatory and analgesic effects in the liver and gallbladder, and therapeutic effects in neurological, cardiovascular and cerebrovascular diseases. The results of the current study demonstrate that geniposide attenuates epilepsy in a mouse model through the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) signaling pathway. A mouse model of epilepsy was induced by maximal electric shock (50 mA, 50 Hz, 1 sec). Epilepsy mice were intragastrically administered with 0, 5, 10 or 20 mg/kg geniposide. Geniposide significantly reduced the incidence and significantly increased the latency of clonic seizures in epileptic mice compared with non-treated epileptic mice (both P<0.01). Geniposide treatment significantly inhibited cyclooxygenase-2 mRNA expression in epilepsy mice (P<0.01). Furthermore, geniposide significantly suppressed the protein expression of activator protein 1, increased the activation of Akt and increased the protein expression of GSK-3β and PI3K in epilepsy mice (all P<0.01). These results suggest that geniposide attenuates epilepsy in mice through the PI3K/Akt/GSK-3β signaling pathway.

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Maturational Regulation and Regional Induction of Cyclooxygenase-2 in Rat Brain: Implications for Alzheimer's Disease

Cited by 163 publications

References 43 publications

Pharmacologic suppression of oxidative damage and dendritic degeneration following kainic acid-induced excitotoxicity in mouse cerebrum

Pharmacologic suppression of oxidative damage and dendritic degeneration following kainic acid-induced excitotoxicity in mouse cerebrum

Potentiation of Excitotoxicity in Transgenic Mice Overexpressing Neuronal Cyclooxygenase-2

Geniposide attenuates epilepsy symptoms in a mouse model through the PI3K/Akt/GSK‑3β signaling pathway

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