The role of NMDA and mGluR5 receptors in calcium mobilization and neurotoxicity of homocysteine in trigeminal and cortical neurons and glial cells

Абушик, П. А.; Niittykoski, Minna; Giniatullina, Raisa; Shakirzyanova, Anastasia; Bart, Geneviève; Fayuk, Dmitriy; Сибаров, Д. А.; Антонов, С. М.; Giniatullin, Rashid

doi:10.1111/jnc.12615

Cited by 72 publications

(61 citation statements)

References 74 publications

(184 reference statements)

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“…With live imaging, we also compared the ability of these compounds to generate Ca 2+ transients in trigeminal neurons and satellite glial cells and to evaluate the action of CGRP on the functional activity of ATP and its dephosphorylated metabolites. As these cultures contained both neurons and glial cells [38], we distinguished neurons from glial cell by the high responsiveness of the former to K + (notice last application in the trace in Fig. 7a).…”

Section: Nucleotide Ca 2+ Signaling In Trigeminal Cellsmentioning

confidence: 99%

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Nucleotide homeostasis and purinergic nociceptive signaling in rat meninges in migraine-like conditions

Yegutkin

Guerrero-Toro

Kılınç

et al. 2016

Purinergic Signalling

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Extracellular ATP is suspected to contribute to migraine pain but regulatory mechanisms controlling pronociceptive purinergic mechanisms in the meninges remain unknown. We studied the peculiarities of metabolic and signaling pathways of ATP and its downstream metabolites in rat meninges and in cultured trigeminal cells exposed to the migraine mediator calcitonin gene-related peptide (CGRP). Under resting conditions, meningeal ATP and ADP remained at low nanomolar levels, whereas extracellular AMP and adenosine concentrations were one-two orders higher. CGRP increased ATP and ADP levels in meninges and trigeminal cultures and reduced adenosine concentration in trigeminal cells. Degradation rates for exogenous nucleotides remained similar in control and CGRP-treated meninges, indicating that CGRP triggers nucleotide release without affecting nucleotide-inactivating pathways. Lead nitrate-based enzyme histochemistry of whole mount meninges revealed the presence of high ATPase, ADPase, and AMPase activities, primarily localized in the medial meningeal artery. ATP and ADP induced large intracellular Ca 2+ transients both in neurons and in glial cells whereas AMP and adenosine were ineffective. In trigeminal glia, ATP partially operated via P2X7 receptors. ATP, but not other nucleotides, activated nociceptive spikes in meningeal trigeminal nerve fibers providing a rationale for high degradation rate of pro-nociceptive ATP. Pronociceptive effect of ATP in meningeal nerves was reproduced by α,β-meATP operating via P2X3 receptors. Collectively, extracellular ATP, which level is controlled by CGRP, can persistently activate trigeminal nerves in meninges which considered as the origin site of migraine headache. These data are consistent with the purinergic hypothesis of migraine pain and suggest new targets against trigeminal pain.

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Section: Nucleotide Ca 2+ Signaling In Trigeminal Cellsmentioning

confidence: 99%

“…Therefore, next, we performed measurements of ATP, ADP, AMP, and adenosine in trigeminal ganglion cultures. Notably, trigeminal cultures consist of both neurons and several types of satellite cells, which are likely contributors to migraine pain [27,38].…”

Section: Basal Level Of Nucleotides In Trigeminal Cells and Effect Ofmentioning

confidence: 99%

Nucleotide homeostasis and purinergic nociceptive signaling in rat meninges in migraine-like conditions

Yegutkin

Guerrero-Toro

Kılınç

et al. 2016

Purinergic Signalling

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“…Hyperhomocysteinemia might contribute to elevate intracellular Ca 2? levels through NMDA and mGluR5 receptors [40]. It can also trigger endothelial dysfunction and pro-coagulation through the involvement of oxidative stress [41].…”

Section: Discussionmentioning

confidence: 99%

Multifactor dimensionality reduction analysis to elucidate the cross-talk between one-carbon and xenobiotic metabolic pathways in multi-disease models

et al. 2015

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Putatively functional polymorphisms of one-carbon and xenobiotic metabolic pathways influence susceptibility for wide spectrum of diseases. The current study was aimed to explore gene-gene interactions among these two metabolic pathways in four diseases i.e. breast cancer, systemic lupus erythematosus (SLE), coronary artery disease (CAD) and Parkinson's disease (PD). Multifactor dimensionality reduction analysis was carried out on four case-control datasets. Cross-talk was observed between one-carbon and xenobiotic pathways in breast cancer (RFC 80 G>A, COMT H108L and TYMS 5'-UTR 28 bp tandem repeat) and SLE (CYP1A1 m1, MTRR 66 A>G and GSTT1). Gene-gene interactions within one-carbon metabolic pathway were observed in CAD (GCPII 1561 C>T, SHMT 1420 C>T and MTHFR 677 C>T) and PD (cSHMT 1420 C>T, MTRR 66 A>G and RFC1 80 G>A). These interaction models showed good predictability of risk for PD (The area under the receiver operating characteristic curve (C) = 0.83) and SLE (C = 0.73); and moderate predictability of risk for breast cancer (C = 0.64) and CAD (C = 0.63). Cross-talk between one-carbon and xenobiotic pathways was observed in diseases with female preponderance. Gene-gene interactions within one-carbon metabolic pathway were observed in diseases with male preponderance.

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“…Homocysteine (Hcy) is an amino acid and several observational studies have shown that Hcy is a risk factor for cardiovascular disease and idiopathic pain, like migraine [32]. Recently, glutamatergic sensitization of trigeminal neurons and satellite glial cells (SGC) by Hcy through NMDA and mGluR5 receptors with a selectivity of effect according to the considered cell has been demonstrated [32].…”

Section: Homocysteinementioning

confidence: 99%

“…Recently, glutamatergic sensitization of trigeminal neurons and satellite glial cells (SGC) by Hcy through NMDA and mGluR5 receptors with a selectivity of effect according to the considered cell has been demonstrated [32]. Furthermore, Hcy leads to production of metabolites (homocysteic acid and cysteine sulfinic acid), acting as NMDA receptors with neurotoxic effects on dopaminergic neurons [33].…”

Section: Homocysteinementioning

confidence: 99%

Role of vitamin B6 in idiopathic burning mouth syndrome: some clinical observations

Dieb

Moreau

Rochefort

et al. 2016

Med Buccale Chir Buccale

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-Introduction:Idiopathic burning mouth syndrome (iBMS) is a chronic oral pain syndrome mainly characterized by a burning sensation in the oral mucosa and an etiopathogenesis that remains unclear, with therapeutic options that are disappointing. Any clinical observation providing insight into the disorder can therefore be of interest. Among metabolic factors, deficiencies of vitamins have been pointed out, but only a few studies have focused on the role of vitamin B6 (vitB6) in this syndrome. In this report, we aimed to highlight the involvement of increased but not decreased vitB6 serum levels in a subgroup of BMS Patients. Patients and Methods: Medical files of patients who attended the chronic orofacial pain consultation, in the dental departement of the Groupe Hospitalier Pitié-Salpêtrière (GHPS) in Paris (France) between 09/03/2008 and 12/19/2015 were retrieved from the hospital database and analyzed. This retrospective study was approved by the board of the dental department and authorization for use of patient data was obtained from the National Personal Data Protection Committee (Commission Nationale de l'Informatique et des Libertés (CNIL)) (#1913570). Results: Seven per-or postmenopausal female patients out of 42 diagnosed with iBMS (17%) displayed an increase in their serum levels of vitB6, one to six times the upper normal limits. There was a statistically significant correlation between pain and vitB6 levels. Moreover, in two patients, the reversal of vitB6 levels to normal values resulted in significant decreases in pain severity. Conclusion: These clinical observations report for the first time a potential implication of elevated vitB6 serum levels in the burning sensation which might be specific to a subgroup of iBMS patients. (# 1913570) pour l'utilisation des données des patients. Résultats : Parmi les 42 patients diagnostiqués iBMS, sept (17%) présentaient des taux sériques de vitB6 sérique plus élevés, jusqu'à 6 fois les valeurs normales. Une corrélation statistiquement significative entre la douleur, évaluée par une échelle numérique simple, et les niveaux vitB6 a été observée. En outre, chez deux patients, le retour à des valeurs normales des taux sériques de vitB6 a donné lieu à une diminution significative de l'intensité douloureuse. Conclusion : Ces observations cliniques rapportent pour la première fois l'implication potentielle de taux sériques élevés de vitB6 dans les sensations de brûlure buccale qui pourraient être spécifiques d'un sous groupe de patients stomatodyniques. Résumé Key words: pyridoxine / pyridoxal 5'-phosphate (PLP) / painMed Buccale Chir Buccale 2017;23:77-83

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The role of NMDA and mGluR5 receptors in calcium mobilization and neurotoxicity of homocysteine in trigeminal and cortical neurons and glial cells

Cited by 72 publications

References 74 publications

Nucleotide homeostasis and purinergic nociceptive signaling in rat meninges in migraine-like conditions

Nucleotide homeostasis and purinergic nociceptive signaling in rat meninges in migraine-like conditions

Multifactor dimensionality reduction analysis to elucidate the cross-talk between one-carbon and xenobiotic metabolic pathways in multi-disease models

Role of vitamin B6 in idiopathic burning mouth syndrome: some clinical observations

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