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Neonicotinoid insecticides are nicotine-derived molecules which exert acute neurotoxic effects over the insect central nervous system by activating nicotinic acetylcholine receptors (nAChRs). However, these receptors are also present in the mammalian central and peripheral nervous system, where the effects of neonicotinoids are faintly known. In mammals, cholinergic synapses are crucial for the control of vascular tone, blood pressure and skeletal muscle contraction. We therefore hypothesized that neonicotinoids could affect cholinergic networks in mammals and sought to highlight functional consequences of acute intoxication in rats with sub-lethal concentrations of the highly used acetamiprid (ACE) and clothianidin (CLO). In this view, we characterized their electrophysiological effects on rat
Joohee Park; Antoine Taly; Jennifer Bourreau; Frédéric De Nardi; Claire Legendre; Daniel Henrion; Nathalie Guérineau; Christian Legros; César Mattei; Hélène Tricoire-Leignel. Partial Agonist Activity of Neonicotinoids on Rat Nicotinic Receptors: Consequences over Epinephrine Secretion and In Vivo Blood Pressure. International Journal of Molecular Sciences 2021, 22, 5106 .
AMA StyleJoohee Park, Antoine Taly, Jennifer Bourreau, Frédéric De Nardi, Claire Legendre, Daniel Henrion, Nathalie Guérineau, Christian Legros, César Mattei, Hélène Tricoire-Leignel. Partial Agonist Activity of Neonicotinoids on Rat Nicotinic Receptors: Consequences over Epinephrine Secretion and In Vivo Blood Pressure. International Journal of Molecular Sciences. 2021; 22 (10):5106.
Chicago/Turabian StyleJoohee Park; Antoine Taly; Jennifer Bourreau; Frédéric De Nardi; Claire Legendre; Daniel Henrion; Nathalie Guérineau; Christian Legros; César Mattei; Hélène Tricoire-Leignel. 2021. "Partial Agonist Activity of Neonicotinoids on Rat Nicotinic Receptors: Consequences over Epinephrine Secretion and In Vivo Blood Pressure." International Journal of Molecular Sciences 22, no. 10: 5106.
Cardiovascular diseases (CVDs) are considered as a major cause of death worldwide. Therefore, identifying and developing therapeutic strategies to treat and reduce the prevalence of CVDs is a major medical challenge. Several drugs used for the treatment of CVDs, such as captopril, emerged from natural products, namely snake venoms. These venoms are complex mixtures of bioactive molecules, which, among other physiological networks, target the cardiovascular system, leading to them being considered in the development and design of new drugs. In this review, we describe some snake venom molecules targeting the cardiovascular system such as phospholipase A2 (PLA2), natriuretic peptides (NPs), bradykinin-potentiating peptides (BPPs), cysteine-rich secretory proteins (CRISPs), disintegrins, fibrinolytic enzymes, and three-finger toxins (3FTXs). In addition, their molecular targets, and mechanisms of action—vasorelaxation, inhibition of platelet aggregation, cardioprotective activities—are discussed. The dissection of their biological effects at the molecular scale give insights for the development of future snake venom-derived drugs.
Jacinthe Frangieh; Mohamad Rima; Ziad Fajloun; Daniel Henrion; Jean-Marc Sabatier; Christian Legros; César Mattei. Snake Venom Components: Tools and Cures to Target Cardiovascular Diseases. Molecules 2021, 26, 2223 .
AMA StyleJacinthe Frangieh, Mohamad Rima, Ziad Fajloun, Daniel Henrion, Jean-Marc Sabatier, Christian Legros, César Mattei. Snake Venom Components: Tools and Cures to Target Cardiovascular Diseases. Molecules. 2021; 26 (8):2223.
Chicago/Turabian StyleJacinthe Frangieh; Mohamad Rima; Ziad Fajloun; Daniel Henrion; Jean-Marc Sabatier; Christian Legros; César Mattei. 2021. "Snake Venom Components: Tools and Cures to Target Cardiovascular Diseases." Molecules 26, no. 8: 2223.
Anatoxin-a (ATX-a) is a neurotoxic alkaloid, produced by several freshwater planktonic and benthic cyanobacteria (CB). Such CB have posed human and animal health issues for several years, as this toxin is able to cause neurologic symptoms in humans following food poisoning and death in wild and domestic animals. Different episodes of animal intoxication have incriminated ATX-a worldwide, as confirmed by the presence of ATX-a-producing CB in the consumed water or biofilm, or the observation of neurotoxic symptoms, which match experimental toxicity in vivo. Regarding toxicity parameters, toxicokinetics knowledge is currently incomplete and needs to be improved. The toxin can passively cross biological membranes and act rapidly on nicotinic receptors, its main molecular target. In vivo and in vitro acute effects of ATX-a have been studied and make possible to draw its mode of action, highlighting its deleterious effects on the nervous systems and its effectors, namely muscles, heart and vessels, and the respiratory apparatus. However, very little is known about its putative chronic toxicity. This review updates available data on ATX-a, from the ecodynamic of the toxin to its physiological and molecular targets.
Simon Colas; Benjamin Marie; Emilie Lance; Catherine Quiblier; Hélène Tricoire-Leignel; César Mattei. Anatoxin-a: Overview on a harmful cyanobacterial neurotoxin from the environmental scale to the molecular target. Environmental Research 2020, 193, 110590 .
AMA StyleSimon Colas, Benjamin Marie, Emilie Lance, Catherine Quiblier, Hélène Tricoire-Leignel, César Mattei. Anatoxin-a: Overview on a harmful cyanobacterial neurotoxin from the environmental scale to the molecular target. Environmental Research. 2020; 193 ():110590.
Chicago/Turabian StyleSimon Colas; Benjamin Marie; Emilie Lance; Catherine Quiblier; Hélène Tricoire-Leignel; César Mattei. 2020. "Anatoxin-a: Overview on a harmful cyanobacterial neurotoxin from the environmental scale to the molecular target." Environmental Research 193, no. : 110590.
Pinnatoxins (PnTXs) are a group of emerging marine biotoxins produced by the benthic dinoflagellate Vulcanodinium rugosum, currently not regulated in Europe or in any other country in the world. In France, PnTXs were detected for the first time in 2011, in mussels from the Ingril lagoon (South of France, Mediterranean coast). Since then, analyses carried out in mussels from this lagoon have shown high concentrations of PnTXs for several months each year. PnTXs have also been detected, to a lesser extent, in mussels from other Mediterranean lagoons and on the Atlantic and Corsican coasts. In the French data, the main analog is PnTX G (low levels of PnTX A are also present in some samples). No cases of PnTXs poisoning in humans have been reported so far in France or anywhere else in the world. In mice, PnTXs induce acute neurotoxic effects, within a few minutes after oral administration. Clinical signs of toxicity include decreased mobility, paralysis of the hind legs, tremors, jumps and breathing difficulties leading to death by respiratory arrest at high doses. The French agency for food safety (ANSES) recently conducted a review of the state of knowledge related to PnTXs and V. rugosum. Based on (i) the clinical signs of toxicity in mice, (ii) the mode of action of PnTXs as nicotinic acetylcholine receptor competitive antagonists and (iii) knowledge on drugs and natural toxins with PnTX-related pharmacology, potential human symptoms have been extrapolated and proposed. In this work, a provisional acute benchmark value for PnTX G of 0.13 μg/kg bw per day has been derived from an oral acute toxicity study in mice. Based on this value and a large shellfish meat portion size of 400g, a concentration lower than 23 μg PnTX G/kg shellfish meat is not expected to result in adverse effects in humans. ANSES recommends taking into account PnTXs in the French official monitoring program for shellfish production and identified data gaps to refine health risk assessment.
Nathalie Arnich; Eric Abadie; Nicolas Delcourt; Valérie Fessard; Jean-Marc Fremy; Vincent Hort; Emmeline Lagrange; Thomas Maignien; Jordi Molgó; Marie-Bénédicte Peyrat; Jean-Paul Vernoux; César Mattei. Health risk assessment related to pinnatoxins in French shellfish. Toxicon 2020, 180, 1 -10.
AMA StyleNathalie Arnich, Eric Abadie, Nicolas Delcourt, Valérie Fessard, Jean-Marc Fremy, Vincent Hort, Emmeline Lagrange, Thomas Maignien, Jordi Molgó, Marie-Bénédicte Peyrat, Jean-Paul Vernoux, César Mattei. Health risk assessment related to pinnatoxins in French shellfish. Toxicon. 2020; 180 ():1-10.
Chicago/Turabian StyleNathalie Arnich; Eric Abadie; Nicolas Delcourt; Valérie Fessard; Jean-Marc Fremy; Vincent Hort; Emmeline Lagrange; Thomas Maignien; Jordi Molgó; Marie-Bénédicte Peyrat; Jean-Paul Vernoux; César Mattei. 2020. "Health risk assessment related to pinnatoxins in French shellfish." Toxicon 180, no. : 1-10.
Pinnatoxins (PnTXs) are emerging neurotoxins that were discovered about 30 years ago. They are solely produced by the marine dinoflagellate Vulcanodinium rugosum, and may be transferred into the food chain, as they have been found in various marine invertebrates, including bivalves. No human intoxication has been reported to date although acute toxicity was induced by PnTxs in rodents. LD50 values have been estimated for the different PnTXs through the oral route. At sublethal doses, all symptoms are reversible, and no neurological sequelae are visible. These symptoms are consistent with impairment of central and peripheral cholinergic network functions. In fact, PnTXs are high-affinity competitive antagonists of nicotinic acetylcholine receptors (nAChRs). Moreover, their lethal effects are consistent with the inhibition of muscle nAChRs, inducing respiratory distress and paralysis. Human intoxication by ingestion of PnTXs could result in various symptoms observed in episodes of poisoning with natural nAChR antagonists. This review updates the available data on PnTX toxicity with a focus on their mode of action on cholinergic networks and suggests the effects that could be extrapolated on human physiology.
Nicolas Delcourt; Emmeline Lagrange; Eric Abadie; Valérie Fessard; Jean-Marc Frémy; Jean-Paul Vernoux; Marie-Bénédicte Peyrat; Thomas Maignien; Nathalie Arnich; Jordi Molgó; César Mattei. Pinnatoxins' Deleterious Effects on Cholinergic Networks: From Experimental Models to Human Health. Marine Drugs 2019, 17, 425 .
AMA StyleNicolas Delcourt, Emmeline Lagrange, Eric Abadie, Valérie Fessard, Jean-Marc Frémy, Jean-Paul Vernoux, Marie-Bénédicte Peyrat, Thomas Maignien, Nathalie Arnich, Jordi Molgó, César Mattei. Pinnatoxins' Deleterious Effects on Cholinergic Networks: From Experimental Models to Human Health. Marine Drugs. 2019; 17 (7):425.
Chicago/Turabian StyleNicolas Delcourt; Emmeline Lagrange; Eric Abadie; Valérie Fessard; Jean-Marc Frémy; Jean-Paul Vernoux; Marie-Bénédicte Peyrat; Thomas Maignien; Nathalie Arnich; Jordi Molgó; César Mattei. 2019. "Pinnatoxins' Deleterious Effects on Cholinergic Networks: From Experimental Models to Human Health." Marine Drugs 17, no. 7: 425.
Etifoxine (EFX) is a non-benzodiazepine psychoactive drug which exhibits anxiolytic effects through a dual mechanism, by directly binding to GABAA receptors (GABAARs) and to the mitochondrial 18-kDa translocator protein, resulting in the potentiation of the GABAergic function. The β subunit subtype plays a key role in the EFX-GABAAR interaction, however this does not explain the anxiolytic effects of this drug. Here, we combined behavioral and electrophysiological experiments to challenge the role of the GABAAR α subunit in the EFX mode of action. After single administrations of anxiolytic doses (25-50 mg/kg, intraperitoneal), EFX did not induce any neurological nor locomotor impairments, unlike the benzodiazepine bromazepam (0.5-1 mg/kg, intraperitoneal). We established the EFX pharmacological profile on heteropentameric GABAARs constructed with α1 to α6 subunit expressed in Xenopus oocyte. Unlike what is known for benzodiazepines, neither the γ nor δ subunits influenced EFX-mediated potentiation of GABA-evoked currents. EFX acted first as a partial agonist on α2β3γ2S, α3β3γ2S, α6β3γ2S and α6β3δ GABAARs, but not on α1β3γ2S, α4β3γ2S, α4β3δ nor α5β3γ2S GABAARs. Moreover, EFX exhibited much higher positive allosteric modulation towards α2β3γ2S, α3β3γ2S and α6β3γ2S than for α1β3γ2S, α4β3γ2S and α5β3γ2S GABAARs. At 20 µM, corresponding to brain concentration at anxiolytic doses, EFX increased GABA potency to the highest extent for α3β3γ2S GABAARs. We built a docking model of EFX on α3β3γ2S GABAARs, which is consistent with a binding site located between α and β subunits in the extracellular domain. In conclusion, EFX preferentially potentiates α2β3γ2S and α3β3γ2S GABAARs, which might support its advantageous anxiolytic/sedative balance.
César Mattei; Antoine Taly; Zineb Soualah; Ophélie Saulais; Daniel Henrion; Nathalie Guerineau; Marc Verleye; Christian Legros. Involvement of the GABAA receptor α subunit in the mode of action of etifoxine. Pharmacological Research 2019, 145, 104250 .
AMA StyleCésar Mattei, Antoine Taly, Zineb Soualah, Ophélie Saulais, Daniel Henrion, Nathalie Guerineau, Marc Verleye, Christian Legros. Involvement of the GABAA receptor α subunit in the mode of action of etifoxine. Pharmacological Research. 2019; 145 ():104250.
Chicago/Turabian StyleCésar Mattei; Antoine Taly; Zineb Soualah; Ophélie Saulais; Daniel Henrion; Nathalie Guerineau; Marc Verleye; Christian Legros. 2019. "Involvement of the GABAA receptor α subunit in the mode of action of etifoxine." Pharmacological Research 145, no. : 104250.
Bee venom is a mixture of several components with proven therapeutic benefits, among which are anti-inflammatory, analgesic, and various cardiovascular conditions. In this work, we analyzed for the first time the proteomic content and biological properties of the crude venom from Apis mellifera syriaca, a honeybee from the Middle East region. Using high-performance liquid chromatography-tandem mass spectrometry, we evidence the venom contains phospholipase A2, hyaluronidase, mast cell-degranulating peptide, adolapin, apamin, and melittin. The latter was purified by solid phase extraction method (SPE) and tested in parallel with crude venom for biological activities. Precisely, crude venom-but not melittin-exhibited antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa strains. Alongside, hemolytic activity was observed in human blood subjected to the venom at high doses. A. mellifera syriaca venom displayed antioxidant activities, and not surprisingly, PLA2 catalytic activity. Eventually, the venom proved to exert antiproliferative effects against MCF-7 and 3T3 cancer cells lines. This first report of a new bee venom opens new avenues for therapeutic uses of bee venoms.
Jacinthe Frangieh; Yahya Salma; Katia Haddad; Cesar Mattei; Christian Legros; Ziad Fajloun; Dany El Obeid. First Characterization of The Venom from Apis mellifera syriaca, A Honeybee from The Middle East Region. Toxins 2019, 11, 191 .
AMA StyleJacinthe Frangieh, Yahya Salma, Katia Haddad, Cesar Mattei, Christian Legros, Ziad Fajloun, Dany El Obeid. First Characterization of The Venom from Apis mellifera syriaca, A Honeybee from The Middle East Region. Toxins. 2019; 11 (4):191.
Chicago/Turabian StyleJacinthe Frangieh; Yahya Salma; Katia Haddad; Cesar Mattei; Christian Legros; Ziad Fajloun; Dany El Obeid. 2019. "First Characterization of The Venom from Apis mellifera syriaca, A Honeybee from The Middle East Region." Toxins 11, no. 4: 191.
Tetrodotoxin (TTX), the mode of action of which has been known since the 1960s, is widely used in pharmacology as a specific inhibitor of voltage-gated sodium channels (Nav channels). This toxin has contributed to the characterization of the allosteric model of the Nav channel, and to discriminating TTX-sensitive and TTX-resistant subtypes. In addition to its role as a pharmacological tool, TTX is now considered a therapeutic molecule, and its development should lead to its use in certain pathologies involving Nav channels, particularly in the field of pain. Specifically, the blockade of Nav channels expressed in nociceptive fibres is one strategy for alleviating pain and its deleterious consequences on health. Recent work has identified, in addition to the Nav1.7, 1.8 and 1.9 channels, the Nav1.1 subtype on dorsal root ganglion (DRG) neurons as a crucial player in mechanical and non-thermal pain. The sensitivity of Nav1.1 to TTX could be exploited at the therapeutic level, especially in chronic pain conditions.
César Mattei. Tetrodotoxin, a Candidate Drug for Nav1.1-Induced Mechanical Pain? Marine Drugs 2018, 16, 72 .
AMA StyleCésar Mattei. Tetrodotoxin, a Candidate Drug for Nav1.1-Induced Mechanical Pain? Marine Drugs. 2018; 16 (2):72.
Chicago/Turabian StyleCésar Mattei. 2018. "Tetrodotoxin, a Candidate Drug for Nav1.1-Induced Mechanical Pain?" Marine Drugs 16, no. 2: 72.
The implication of the cyanotoxin β-N-methylamino-l-alanine (BMAA) in long-lasting neurodegenerative disorders is still a matter of controversy. It has been alleged that chronic ingestion of BMAA through the food chain could be a causative agent of amyotrophic lateral sclerosis (ALS) and several related pathologies including Parkinson syndrome. Both in vitro and in vivo studies of the BMAA mode of action have focused on different molecular targets, demonstrating its toxicity to neuronal cells, especially motoneurons, and linking it to human neurodegenerative diseases. Historically, the hypothesis of BMAA-induced excitotoxicity following the stimulation of glutamate receptors has been established. However, in this paradigm, most studies have shown acute, rather than chronic effects of BMAA. More recently, the interaction of this toxin with neuromelanin, a pigment present in the nervous system, has opened a new research perspective. The issues raised by this toxin are related to its kinetics of action, and its possible incorporation into cellular proteins. It appears that BMAA neurotoxic activity involves different targets through several mechanisms known to favour the development of neurodegenerative processes.
Nicolas Delcourt; Thomas Claudepierre; Thomas Maignien; Nathalie Arnich; César Mattei. Cellular and Molecular Aspects of the β-N-Methylamino-l-alanine (BMAA) Mode of Action within the Neurodegenerative Pathway: Facts and Controversy. Toxins 2017, 10, 6 .
AMA StyleNicolas Delcourt, Thomas Claudepierre, Thomas Maignien, Nathalie Arnich, César Mattei. Cellular and Molecular Aspects of the β-N-Methylamino-l-alanine (BMAA) Mode of Action within the Neurodegenerative Pathway: Facts and Controversy. Toxins. 2017; 10 (1):6.
Chicago/Turabian StyleNicolas Delcourt; Thomas Claudepierre; Thomas Maignien; Nathalie Arnich; César Mattei. 2017. "Cellular and Molecular Aspects of the β-N-Methylamino-l-alanine (BMAA) Mode of Action within the Neurodegenerative Pathway: Facts and Controversy." Toxins 10, no. 1: 6.
Stéphanie Pineau; Christian Legros; César Mattei. The Medical use of Lemon Balm (Melissa officinalis) and Valerian (Valeriana officinalis) as Natural Sedatives: Insight into their Interactions with GABA Transmission. International Journal of Clinical Pharmacology & Pharmacotherapy 2016, 1, 1 .
AMA StyleStéphanie Pineau, Christian Legros, César Mattei. The Medical use of Lemon Balm (Melissa officinalis) and Valerian (Valeriana officinalis) as Natural Sedatives: Insight into their Interactions with GABA Transmission. International Journal of Clinical Pharmacology & Pharmacotherapy. 2016; 1 (2):1.
Chicago/Turabian StyleStéphanie Pineau; Christian Legros; César Mattei. 2016. "The Medical use of Lemon Balm (Melissa officinalis) and Valerian (Valeriana officinalis) as Natural Sedatives: Insight into their Interactions with GABA Transmission." International Journal of Clinical Pharmacology & Pharmacotherapy 1, no. 2: 1.
Insect nicotinic acetylcholine receptors (nAChRs) represent a major target of insecticides, belonging to the neonicotinoid family. However, the pharmacological profile of native nAChRs is poorly documented, mainly because of a lack of knowledge of their subunit stoichiometry, their tissue distribution and the weak access to nAChR-expressing cells. In addition, the expression of insect nAChRs in heterologous systems remains hard to achieve. Therefore, the structure–activity characterization of nAChR-targeting insecticides is made difficult. The objective of the present study was to characterize insect nAChRs by an electrophysiological approach in a heterologous system naturally devoid of these receptors to allow a molecular/cellular investigation of the mode of action of neonicotinoids. Methods To overcome impediments linked to the expression of insect nAChR mRNA or cDNA, we chose to inject insect membranes from the pea aphid (Acyrthosiphon pisum) into Xenopus oocytes. This microtransplantation technique was designed to gain access to native nAChRs embedded in their membrane, through direct stimulation with nicotinic agonists. Results We provide evidence that an enriched-nAChR membrane allows us to characterize native receptors. The presence of such receptors was confirmed with fluorescent α-BgTX labeling. Electrophysiological recordings of nicotine-induced inward currents allowed us to challenge the presence of functional nAChR. We compared the effect of nicotine (NIC) with clothianidin (CLO) and we assessed the effect of thiamethoxam (TMX). Discussion This technique has been recently highlighted with mammalian and human material as a powerful functional approach, but has, to our knowledge, never been used with insect membrane. In addition, the use of the insect membrane microtransplantation opens a new and original way for pharmacological screening of neurotoxic insecticides, including neonicotinoids. Moreover, it might also be a powerful tool to investigate the pharmacological properties of insect nAChR.
Lucille Crespin; Christian Legros; Olivier List; Hélène Tricoire-Leignel; César Mattei. Injection of insect membrane in Xenopus oocyte: An original method for the pharmacological characterization of neonicotinoid insecticides. Journal of Pharmacological and Toxicological Methods 2016, 77, 10 -16.
AMA StyleLucille Crespin, Christian Legros, Olivier List, Hélène Tricoire-Leignel, César Mattei. Injection of insect membrane in Xenopus oocyte: An original method for the pharmacological characterization of neonicotinoid insecticides. Journal of Pharmacological and Toxicological Methods. 2016; 77 ():10-16.
Chicago/Turabian StyleLucille Crespin; Christian Legros; Olivier List; Hélène Tricoire-Leignel; César Mattei. 2016. "Injection of insect membrane in Xenopus oocyte: An original method for the pharmacological characterization of neonicotinoid insecticides." Journal of Pharmacological and Toxicological Methods 77, no. : 10-16.
Voltage-gated sodium channels (Nav) are key components for nerve excitability. They initiate and propagate the action potential in excitable cells, throughout the central and peripheral nervous system, thus enabling a variety of physiological functions to be achieved. The rising phase of the action potential is driven by the opening of Nav channels which activate rapidly and carry Na(+) ions in the intracellular medium, and ends with the Na(+) current inactivation. The biophysical properties of these channels have been elucidated, through the use of pharmacological agents that disrupt the molecular mechanism of the channel functioning. Among them, marine toxins produced by venomous animals or microorganisms have been crucial to map the different allosteric binding sites of the channels, understand their mode of action and represent an emerging source of therapeutic agents to alleviate or cure Na(+) channels-linked human diseases. In this article, we review recent discoveries on the molecular and biophysical properties of the Na(+) channel as a target for marine neurotoxins, and present the ongoing developments of pharmacological agents as therapeutic tools.
César Mattei; Christian Legros. The voltage-gated sodium channel: A major target of marine neurotoxins. Toxicon 2014, 91, 84 -95.
AMA StyleCésar Mattei, Christian Legros. The voltage-gated sodium channel: A major target of marine neurotoxins. Toxicon. 2014; 91 ():84-95.
Chicago/Turabian StyleCésar Mattei; Christian Legros. 2014. "The voltage-gated sodium channel: A major target of marine neurotoxins." Toxicon 91, no. : 84-95.
Evelyne Benoit; César Mattei; Julien Barbier; Pascale Marchot; Jordi Molgó; Denis Servent. Special Issue on “freshwater and marine toxins”. Toxicon 2014, 91, 1 -4.
AMA StyleEvelyne Benoit, César Mattei, Julien Barbier, Pascale Marchot, Jordi Molgó, Denis Servent. Special Issue on “freshwater and marine toxins”. Toxicon. 2014; 91 ():1-4.
Chicago/Turabian StyleEvelyne Benoit; César Mattei; Julien Barbier; Pascale Marchot; Jordi Molgó; Denis Servent. 2014. "Special Issue on “freshwater and marine toxins”." Toxicon 91, no. : 1-4.
International audienceCiguatoxins, mainly produced by benthic dinoflagellate Gambierdiscus species, are responsible for a complex human poisoning known as ciguatera. Previous pharmacological studies revealed that these toxins activate voltage-gated Na+ channels. In frog nodes of Ranvier, ciguatoxins induce spontaneous and repetitive action potentials (APs) and increase axonal volume that may explain alterations of nerve functioning in intoxicated humans. The present study aimed determining the ionic mechanisms involved in Pacific ciguatoxin-1B (P-CTX-1B)-induced membrane hyperexcitability and subsequent volume increase in frog nodes of Ranvier, using electrophysiology and confocal microscopy. The results reveal that P-CTX-1B action is not dependent on external Cl- ions since it was not affected by substituting Cl- by methylsulfate ions. In contrast, substitution of external Na+ by Li+ ions suppressed spontaneous APs and prevented nodal swelling. This suggests that P-CTX-1B-modified Na+ channels are not selective to Li+ ions and/or are blocked by these ions, and that Na+ influx through Na+ channels opened during spontaneous APs is required for axonal swelling. The fact that the K+ channel blocker tetraethylammonium modified, but did not suppress, spontaneous APs and greatly reduced nodal swelling induced by P-CTX-1B indicates that K+ efflux might also be involved. This is supported by the fact that P-CTX-1B, when tested in the presence of both tetraethylammonium and the K+ ionophore valinomycin, produced the characteristic nodal swelling. It is concluded that, during the action of P-CTX-1B, water movements responsible for axonal swelling depend on both Na+ influx and K+ efflux. These results pave the way for further studies regarding ciguatera treatment
César Mattei; Jordi Molgó; Evelyne Benoit. Involvement of both sodium influx and potassium efflux in ciguatoxin-induced nodal swelling of frog myelinated axons. Neuropharmacology 2014, 85, 417 -426.
AMA StyleCésar Mattei, Jordi Molgó, Evelyne Benoit. Involvement of both sodium influx and potassium efflux in ciguatoxin-induced nodal swelling of frog myelinated axons. Neuropharmacology. 2014; 85 ():417-426.
Chicago/Turabian StyleCésar Mattei; Jordi Molgó; Evelyne Benoit. 2014. "Involvement of both sodium influx and potassium efflux in ciguatoxin-induced nodal swelling of frog myelinated axons." Neuropharmacology 85, no. : 417-426.
International audienceCaribbean ciguatoxin-1 (C-CTX-1) induced, after about 1h exposure, muscle membrane depolarisation and repetitive post-synaptic action potentials (APs) in frog neuromuscular preparations. This depolarising effect was also observed in a Ca(2+)-free medium with a strong enhancement of spontaneous quantal transmitter release, compared with control conditions. The ciguatoxin-induced increase in release could be accelerated when Ca(2+) was present in the extracellular medium. C-CTX-1 also enhanced nerve-evoked quantal acetylcholine (ACh) release. At normal neuromuscular junctions loaded with the fluorescent dye FM1-43, C-CTX-1 induced swelling of nerve terminals, an effect that was reversed by hyperosmotic D-mannitol. In myelinated axons, C-CTX-1 increased nodal membrane excitability, inducing spontaneous and repetitive APs. Also, the toxin enlarged the repolarising phase of APs in control and tetraethylammonium-treated axons. Overall, our data suggest that C-CTX-1 affects nerve excitability and neurotransmitter release at nerve terminals. We conclude that C-CTX-1-induced up-regulation of Na(+) channels and the inhibition of K(+) channels, at low nanomolar concentrations, produce a variety of functional dysfunctions that are in part responsible for the human muscle skeletal symptoms observed in ciguatera. All these dysfunctions seem to result from the subtle balance between ionic currents, intracellular Na(+) and Ca(2+) concentrations, and engaged second messengers
César Mattei; Michel Marquais; Sébastien Schlumberger; Jordi Molgó; Jean-Paul Vernoux; Richard J. Lewis; Evelyne Benoit. Analysis of Caribbean ciguatoxin-1 effects on frog myelinated axons and the neuromuscular junction. Toxicon 2010, 56, 759 -767.
AMA StyleCésar Mattei, Michel Marquais, Sébastien Schlumberger, Jordi Molgó, Jean-Paul Vernoux, Richard J. Lewis, Evelyne Benoit. Analysis of Caribbean ciguatoxin-1 effects on frog myelinated axons and the neuromuscular junction. Toxicon. 2010; 56 (5):759-767.
Chicago/Turabian StyleCésar Mattei; Michel Marquais; Sébastien Schlumberger; Jordi Molgó; Jean-Paul Vernoux; Richard J. Lewis; Evelyne Benoit. 2010. "Analysis of Caribbean ciguatoxin-1 effects on frog myelinated axons and the neuromuscular junction." Toxicon 56, no. 5: 759-767.
Synapses are specialised structures where interneuronal communication takes place. Not only brain function is absolutely dependent on synaptic activity, but also most of our organs are intimately controlled by synaptic activity. Synapses re therefore an ideal target to act upon and poisonous species have evolved fascinating neurotoxins capable of shutting down neuronal communication by blocking or activating essential components of the synapse. By hijacking key proteins of the communication machinery, neurotoxins are therefore extremely valuable tools that have, in turn, greatly helped our understanding of synaptic biology. Moreover, analysis and understanding of the molecular strategy used by certain neurotoxins has allowed the design of entirely new classes of drugs acting on specific targets with high selectivity and efficacy. This chapter will discuss the different classes of marine neurotoxins, their effects on neurotransmitter release and how they act to incapacitate key steps in the process leading to synaptic vesicle fusion.
Frédéric A. Meunier; César Mattei; Jordi Molgó. Marine Toxins Potently Affecting Neurotransmitter Release. Marine Toxins as Research Tools 2009, 46, 159 -186.
AMA StyleFrédéric A. Meunier, César Mattei, Jordi Molgó. Marine Toxins Potently Affecting Neurotransmitter Release. Marine Toxins as Research Tools. 2009; 46 ():159-186.
Chicago/Turabian StyleFrédéric A. Meunier; César Mattei; Jordi Molgó. 2009. "Marine Toxins Potently Affecting Neurotransmitter Release." Marine Toxins as Research Tools 46, no. : 159-186.
Frederic A. Meunier; Gilles Ouanounou; César Mattei; Pascal Chameau; Cesare Colasante; Yuri A. Ushkaryov; J. Oliver Dolly; Arnold S. Kreger; Jordi Molgó; Edward J. Massaro. Secretagogue Activity of Trachynilysin, a Neurotoxic Protein Isolated from Stonefish (Synanceia trachynis) Venom. Handbook of Neurotoxicology 2003, 595 -616.
AMA StyleFrederic A. Meunier, Gilles Ouanounou, César Mattei, Pascal Chameau, Cesare Colasante, Yuri A. Ushkaryov, J. Oliver Dolly, Arnold S. Kreger, Jordi Molgó, Edward J. Massaro. Secretagogue Activity of Trachynilysin, a Neurotoxic Protein Isolated from Stonefish (Synanceia trachynis) Venom. Handbook of Neurotoxicology. 2003; ():595-616.
Chicago/Turabian StyleFrederic A. Meunier; Gilles Ouanounou; César Mattei; Pascal Chameau; Cesare Colasante; Yuri A. Ushkaryov; J. Oliver Dolly; Arnold S. Kreger; Jordi Molgó; Edward J. Massaro. 2003. "Secretagogue Activity of Trachynilysin, a Neurotoxic Protein Isolated from Stonefish (Synanceia trachynis) Venom." Handbook of Neurotoxicology , no. : 595-616.
Evelyne Benoit; Cesar Mattei; Gilles Ouanounou; Frederic A Meunier; Dusan Suput; Frederic Le Gall; Michel Marquais; Marie Y Dechraoui; Jordi Molgo. Ionic mechanisms involved in the nodal swelling of myelinated axons caused by marine toxins. Cellular & Molecular Biology Letters 2002, 7, 1 .
AMA StyleEvelyne Benoit, Cesar Mattei, Gilles Ouanounou, Frederic A Meunier, Dusan Suput, Frederic Le Gall, Michel Marquais, Marie Y Dechraoui, Jordi Molgo. Ionic mechanisms involved in the nodal swelling of myelinated axons caused by marine toxins. Cellular & Molecular Biology Letters. 2002; 7 (2):1.
Chicago/Turabian StyleEvelyne Benoit; Cesar Mattei; Gilles Ouanounou; Frederic A Meunier; Dusan Suput; Frederic Le Gall; Michel Marquais; Marie Y Dechraoui; Jordi Molgo. 2002. "Ionic mechanisms involved in the nodal swelling of myelinated axons caused by marine toxins." Cellular & Molecular Biology Letters 7, no. 2: 1.
Cesar Mattei; Marie‐Yasmine Dechraoui; Jordi Molgo; Frederic A. Meunier; Anne‐Marie Legrand; Evelyne Benoit. Neurotoxins targetting receptor site 5 of voltage‐dependent sodium channels increase the nodal volume of myelinated axons. Journal of Neuroscience Research 1999, 55, 666 -673.
AMA StyleCesar Mattei, Marie‐Yasmine Dechraoui, Jordi Molgo, Frederic A. Meunier, Anne‐Marie Legrand, Evelyne Benoit. Neurotoxins targetting receptor site 5 of voltage‐dependent sodium channels increase the nodal volume of myelinated axons. Journal of Neuroscience Research. 1999; 55 (6):666-673.
Chicago/Turabian StyleCesar Mattei; Marie‐Yasmine Dechraoui; Jordi Molgo; Frederic A. Meunier; Anne‐Marie Legrand; Evelyne Benoit. 1999. "Neurotoxins targetting receptor site 5 of voltage‐dependent sodium channels increase the nodal volume of myelinated axons." Journal of Neuroscience Research 55, no. 6: 666-673.
The effects of a C57 type ciguatoxin (CTX-3C) and two types of brevetoxins (PbTx-1 and PbTx-3), known to bind to receptor site 5 of the neuronal voltage-dependent Na+ channel-protein, were studied on the morphology of living frog myelinated axons using confocal laser scanning microscopy. During the action of CTX-3C, PbTx-1, and PbTx-3 (10–50 nM), a marked swelling of nodes of Ranvier was observed without apparent modification of internodal parts of axons. In all cases, toxin-induced nodal swelling attained a steady-state within 75–100 min that was well maintained during an additional 90–115 min. The nodal swelling was reversed by an external hyperosmotic solution containing 100 mM D-mannitol and could be completely prevented by blocking voltage-dependent Na+ channels with 1 μM tetrodotoxin. It is suggested that CTX-3C, PbTx-1, and PbTx-3 by activating Na+ channels cause a continuous Na+ entry into axons, increasing internal Na+ concentration. Such an increase directly or indirectly disturbs the osmotic equilibrium between intra- and extra-axonal media, resulting in an influx of water, which is responsible for the long-lasting nodal swelling. Similar results were previously reported with two C60 type ciguatoxins (CTX-1B and CTX-4B). Thus, it is concluded that the four types of toxins targetting receptor site 5 of neuronal voltage-dependent Na+ channels, not only enhance nerve membrane excitability but also, on a long-term basis, cause a marked increase in the axonal volume. J. Neurosci. Res. 55:666–673, 1999.
César Mattei; Marie-Yasmine Dechraoui; Jordi Molgó; Frédéric A. Meunier; Anne-Marie Legrand; Evelyne Benoit. Neurotoxins targetting receptor site 5 of voltage-dependent sodium channels increase the nodal volume of myelinated axons. Journal of Neuroscience Research 1999, 55, 666 -673.
AMA StyleCésar Mattei, Marie-Yasmine Dechraoui, Jordi Molgó, Frédéric A. Meunier, Anne-Marie Legrand, Evelyne Benoit. Neurotoxins targetting receptor site 5 of voltage-dependent sodium channels increase the nodal volume of myelinated axons. Journal of Neuroscience Research. 1999; 55 (6):666-673.
Chicago/Turabian StyleCésar Mattei; Marie-Yasmine Dechraoui; Jordi Molgó; Frédéric A. Meunier; Anne-Marie Legrand; Evelyne Benoit. 1999. "Neurotoxins targetting receptor site 5 of voltage-dependent sodium channels increase the nodal volume of myelinated axons." Journal of Neuroscience Research 55, no. 6: 666-673.