Synaptic activation of NF-kappa B by glutamate in cerebellar granule neurons in vitro.

Guerrini, Luisa; Blasi, Francesco; Denis-Donini, S.

doi:10.1073/pnas.92.20.9077

Cited by 263 publications

(183 citation statements)

References 27 publications

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“…In post-mortem tissue from patients with neurodegenerative disease or cultured Expression profiling of NMDA receptor antagonists in brain M Marvanová et al neurons exposed to neurotoxic stimuli, increased NF-kB activity in cells has been reported (Kaltschmidt et al, 1995;Terai et al, 1996;Hunot et al, 1997). Furthermore, several studies have demonstrated that stimulation of both NMDA and non-NMDA glutamate receptors strongly stimulate NF-kB in vitro (Guerrini et al, 1995;Kaltschmidt et al, 1995). Additionally, another gene involved in immune and inflammatory responses, prostaglandin EP2 receptor (Narumiya et al, 1999), was downregulated.…”

Section: Discussionmentioning

confidence: 99%

Identification of Genes Regulated by Memantine and MK-801 in Adult Rat Brain by cDNA Microarray Analysis

Marvanová

Lakso

Wong

2004

Neuropsychopharmacol

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In this study, we monitored gene expression profiles using cDNA microarrays after an acute systemic administration of the high affinity N-methyl-D-aspartate (NMDA) uncompetitive antagonist MK-801 (1 mg/kg; 4 h), and the clinically used moderate affinity antagonist memantine (25 mg/kg; 4 h) in adult rat brains. From a microarray containing 1090 known genes, 13 genes were regulated by both treatments of which 12 were upregulated and one was downregulated. In addition, 28 and 34 genes were regulated (X1.5-or p0.67-fold change) by either memantine or MK-801, respectively. Genes commonly regulated by both treatments and not previously reported were confirmed by in situ hybridization (ISH) and include regenerating liver inhibitory factor-1 (RL/IF-1), GDP-dissociation inhibitor 1 (GDI-1), neural visinin Ca 2 þ -binding protein 2 (NVP-2), neuromedin B receptor, and Na þ /K þ transporting ATPase 2b. ISH with memantine (5-50 mg/kg) revealed regulation of these genes in other cortical and hippocampal regions. RL/IF-1 induction occurred at 1 h and returned to basal levels by 8 h, consistent with the profile of an immediate early gene. Western blot analysis showed increases (B30-65%) in GDI-1 protein present in both cytosolic and membrane fractions that were significant in the 84-kDa Rab bound form, suggesting that memantine influences Ras-like GTPase function. Genes regulated by a 5 mg/kg dose of memantine might be important in its therapeutic effects. These findings increase the number of known, differentially altered genes after treatment of uncompetitive NMDA receptor antagonists and suggest broader actions of these agents than previously realized.

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Section: Discussionmentioning

confidence: 99%

Identification of Genes Regulated by Memantine and MK-801 in Adult Rat Brain by cDNA Microarray Analysis

Marvanová

Lakso

Wong

2004

Neuropsychopharmacol

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“…In neurons, the most common NF-kB complex appears to consist of p65, p50 and IkBa. [2][3][4][5] However, other complexes are present in neurons and their subunit composition may vary depending upon factors such as the developmental state of the neurons and their location within the nervous system. 6,7 The canonical mechanism of NF-kB activation involves phosphorylation of the inhibitory IkB subunit by the IkB kinase complex (IKK); 8 phosphorylation targets IkB for ubiquitination and subsequent proteasomal degradation, thereby releasing the active NF-kB factor dimer ( Figure 1).…”

Section: The Basics Activation Of Nf-jb In Neuronsmentioning

confidence: 99%

“…A growing list of signals that can activate NF-kB in neurons includes tumor necrosis factor-a (TNF), 9 the excitatory neurotransmitter glutamate, 3 nerve growth factor (NGF), 10,11 activity-dependent neurotrophic factor (ADNF), 12 a secreted form of amyloid precursor protein 13 and cell adhesion molecules. 14 These molecules can activate NF-kB through coupling to kinase cascades including calcium/calmodulindependent kinase II, 15 Akt 16,17 and protein kinase C 18 ( Figure 2).…”

Section: The Basics Activation Of Nf-jb In Neuronsmentioning

confidence: 99%

“…One or more of the latter signaling pathways is likely to account for the high constitutive activity of NF-kB in neurons compared to nonexcitable cells. 3,15,19 Dimer composition and transcriptional regulation NF-kB regulates many promoters containing variations in a highly divergent consensus DNA-binding sequence (the kB site). Mice deficient in single subunits of the NF-kB family show distinct phenotypes and this translates into both qualitative and quantitative differences in target gene expression as a result of transcriptional regulation by different dimers.…”

Section: The Basics Activation Of Nf-jb In Neuronsmentioning

confidence: 99%

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Roles for NF-κB in nerve cell survival, plasticity, and disease

2006

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Here we review evidence of roles for NF-jB in the regulation of developmental and synaptic plasticity, and cell survival in physiological and pathological settings. Signaling pathways modulating NF-jB activity include those engaged by neurotrophic factors, neurotransmitters, electrical activity, cytokines, and oxidative stress. Emerging findings support a pivotal role for NF-jB as a mediator of transcription-dependent enduring changes in the structure and function of neuronal circuits. Distinct subunits of NF-jB may uniquely affect cognition and behavior by regulating specific target genes. NF-jB activation can prevent the death of neurons by inducing the production of antiapoptotic proteins such as Bcl-2, IAPs and manganese superoxide dismutase (Mn-SOD). Recent findings indicate that NF-jB plays important roles in disorders such as epilepsy, stroke, Alzheimer's and Parkinson's diseases, as well as oncogenesis. Molecular pathways upstream and downstream of NF-jB in neurons are being elucidated and may provide novel targets for therapeutic intervention in various neurological disorders.

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“…Since it has been found that stimulation of glutamate receptors after excitatory amino acids (EAAs) released during stress leads to the activation of NF-kB in neurons (Guerrini et al, 1995;Kaltschmidt et al, 1995), we decided to explore this possibility. The NMDA receptor blocker MK-801 (0.2 mg/kg) decreases both stress-induced PGE 2 accumulation and COX-2 expression (Figure 3a and b, respectively).…”

Section: Mechanisms Of Cox-2 Expression In Stressmentioning

confidence: 99%

Induction of Cyclooxygenase-2 Accounts for Restraint Stress-Induced Oxidative Status in Rat Brain

Madrigal

Moro

Lizasoaín

et al. 2003

Neuropsychopharmacol

135

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Cyclooxygenase (COX) is the rate-limiting enzyme in the metabolism of arachidonic acid into prostanoids. Although it is constitutively expressed in brain neurons, the inducible isoform (COX-2) is also upregulated in pathological conditions such as seizures, ischemia or some degenerative diseases. To assess whether COX-2 is regulated after stress, we have used adult male Wistar rats, some of which were immobilized during 6 h. An increase in PGE 2 concentration occurs in brain cortex after 2-6 h of the onset of stress as well as an enhancement of COX-2 protein. Immunohistochemical studies indicate that COX-2 is expressed in the cortex and hippocampus after stress in cells with morphology of neurons. Administration of PDTC (150 mg/kg), an inhibitor of the transcription factor NF-kB or MK-801 (0.2 mg/kg), an N-methyl-D-aspartate receptor blocker, prevents both stress-induced increase in COX-2 activity and protein levels, suggesting an implication of these factors in the mechanism by which stress induces COX-2 in brain. To assess if COX-2 accounts for the oxidative status seen in brain after stress, a group of animals were i.p. injected with NS-398, a specific COX-2 inhibitor 1 h prior to the onset of stress. NS-398 (5 mg/kg) decreases stress-induced malondialdehyde accumulation in cortex as well as prevents the stressinduced oxidation of glutathione. Finally, NS-398 reduced Ca 2+ -independent inducible nitric oxide synthase (iNOS, NOS-2) activity and lowered the stress-induced accumulation of NO metabolite levels in cortex. These effects of NS-398 seem to be due to the specific inhibition of COX-2, since it has no effect on stress-induced corticosterone release, glutamate release, and NF-kB activation. These findings are discussed as possible damaging and/or adaptive roles for stress-induced COX-2 in the brain.

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Synaptic activation of NF-kappa B by glutamate in cerebellar granule neurons in vitro.

Cited by 263 publications

References 27 publications

Identification of Genes Regulated by Memantine and MK-801 in Adult Rat Brain by cDNA Microarray Analysis

Identification of Genes Regulated by Memantine and MK-801 in Adult Rat Brain by cDNA Microarray Analysis

Roles for NF-κB in nerve cell survival, plasticity, and disease

Induction of Cyclooxygenase-2 Accounts for Restraint Stress-Induced Oxidative Status in Rat Brain

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