Michel Vignes | Université de Montpellier (original) (raw)

Papers by Michel Vignes

British Journal of Pharmacology

Despite a growing awareness, annual losses of honeybee colonies worldwide continue to reach threa... more Despite a growing awareness, annual losses of honeybee colonies worldwide continue to reach threatening levels for food safety and global biodiversity. Among the biotic and abiotic stresses probably responsible for these losses, pesticides, including those targeting ionotropic GABA receptors, are one of the major drivers. Most insect genomes include the ionotropic GABA receptor subunit gene, Rdl, and two GABA‐like receptor subunit genes, Lcch3 and Grd. Most studies have focused on Rdl which forms homomeric GABA‐gated chloride channels, and a complete analysis of all possible molecular combinations of GABA receptors is still lacking.

International Journal of Neuropsychopharmacology, 2016

Background: Cocaine addiction continues to be a major heath concern, and despite public health in... more Background: Cocaine addiction continues to be a major heath concern, and despite public health intervention there is a lack of efficient pharmacological treatment options. A newly identified potential target are the group I metabotropic glutamate receptors, with allosteric modulators showing particular promise. Methods: We evaluated the capacity of group I metabotropic glutamate receptors to induce functional responses in ex vivo striatal slices from rats with (1) acute cocaine self-administration, (2) chronic cocaine self-administration, and (3) 60 days cocaine self-administration withdrawal by Western blot and extracellular recordings of synaptic transmission. Results: We found that striatal group I metabotropic glutamate receptors are the principal mediator of the mGluR 1/5 agonist (RS)-3,5-dihydroxyphenylglycine-induced cAMP responsive-element binding protein phosphorylation. Both acute and chronic cocaine self-administration blunted group I metabotropic glutamate receptor effects on cAMP responsive-element binding protein phosphorylation in the striatum, which correlated with the capacity to induce long-term depression, an effect that was maintained 60 days after chronic cocaine self-administration withdrawal. In the nucleus accumbens, the principal brain region mediating the rewarding effects of drugs, chronic cocaine self-administration blunted group I metabotropic glutamate receptor stimulation of extracellular signal-regulated protein kinases 1/2 and cAMP responsive-element binding protein.

Peptide neurotoxins found in animal venoms have gained great interest in the field of neurotransm... more Peptide neurotoxins found in animal venoms have gained great interest in the field of neurotransmission. As they are high affinity ligands for calcium, potassium and sodium channels, they have become useful tools for studying channel structure and activity. Peptide neurotoxins represent the clinical potential of ion-channel modulators across several therapeutic fields, especially in developing new strategies for treatment of ion channel-related diseases. The aim of this review is to overview the latest updates in the domain of peptide neurotoxins that affect voltage-gated calcium channels, with a special focus on -agatoxins.

Lab on a Chip

Microfluidic devices were coupled with custom MEA and used for co-culture of human motor neurons ... more Microfluidic devices were coupled with custom MEA and used for co-culture of human motor neurons and muscles. This allowed to assess human NMJ activity by electrical stimulation of axons and recording of subsequent muscle action potentials.

Journal of Biological Chemistry

Human molecular genetics, 2018

Huntington's disease (HD) is caused by a mutation in the Huntingtin (HTT) protein. We previou... more Huntington's disease (HD) is caused by a mutation in the Huntingtin (HTT) protein. We previously reported that the 23aa peptide of HTT protein, P42, is preventing HD pathological phenotypes, such as aggregation, reduction of motor performances and neurodegeneration. A systemic treatment with P42 during the pre-symptomatic phase of the disease showed therapeutic potential in R6/2 mice. We here tested P42 effects when administered during the post-symptomatic phase. The P42 treatment alleviated deficits in motor performances, even when symptoms have already started. Because changes in the level and activity of brain-derived neurotrophic factor (BDNF) have been shown to play a central role in HD, we analysed the influence of P42 on BDNF deficit and associated phenotypes. Our data suggest that P42 is involved in the spatio-temporal control of bdnf and trkB mRNA and their protein levels. Related to this enhancement of BDNF-TrkB signalling, R6/2 mice treated with P42, exhibit reduced a...

Neurochemical research, Jan 20, 2018

Maternal immune challenge has proved to induce moderate to severe behavioral disabilities in the ... more Maternal immune challenge has proved to induce moderate to severe behavioral disabilities in the offspring. Cognitive/behavioral deficits are supported by changes in synaptic plasticity in different brain areas. We have reported previously that prenatal exposure to bacterial LPS could induce inhibition of hippocampal long-term potentiation (LTP) in the CA1 area of the juvenile/adult male offspring associated with spatial learning inabilities. Nevertheless, deficits in plasticity could be observed at earlier stages as shown by the early loss of long-term depression (LTD) in immature animals. Moreover, aberrant forms of plasticity were also evidenced such as the transient occurrence of LTP instead of LTD in 15-25 day-old animals. This switch from LTD to LTP seemed to involve the activation of metabotropic glutamate receptor subtype 1 and 5 (mGlu1/5). We have thus investigated here whether the long-term depression elicited by the direct activation of these receptors (mGlu-LTD) with a s...

ACS chemical neuroscience, Aug 16, 2017

l-Theanine (or l-γ-N-ethyl-glutamine) is the major amino acid found in Camellia sinensis. It has ... more l-Theanine (or l-γ-N-ethyl-glutamine) is the major amino acid found in Camellia sinensis. It has received much attention because of its pleiotropic physiological and pharmacological activities leading to health benefits in humans, especially. We describe here a new, easy, efficient, and environmentally friendly chemical synthesis of l-theanine and l-γ-N-propyl-Gln and their corresponding d-isomers. l-Theanine, and its derivatives obtained so far, exhibited partial coagonistic action at N-methyl-d-aspartate (NMDA) receptors, with no detectable agonist effect at other glutamate receptors, on cultured hippocampal neurons. This activity was retained on NMDA receptors expressed in Xenopus oocytes. In addition, both GluN2A and GluN2B containing NMDA receptors were equally modulated by l-theanine. The stereochemical change from l-theanine to d-theanine along with the substitution of the ethyl for a propyl moiety in the γ-N position of l- and d-theanine significantly enhanced the biological...

Brain Research, 1998

Type 2 transglutaminase (Tg), which catalyzes the covalent cross-linking of cytoplasmic proteins ... more Type 2 transglutaminase (Tg), which catalyzes the covalent cross-linking of cytoplasmic proteins during apoptosis, also functions as the α subunit of a heterodimeric G-protein (Gh) which can activate phospholipase C-δ1 during the signal transduction pathway linked to α1-adrenoreceptors. Continued stimulation of rat forebrain ventricular zone (VZ) germinal cells with the α1-agonist phenylephrine during development in vitro suppresses apoptosis and promotes

European Journal of Neuroscience, Sep 1, 1995

The regulation of intracellular Ca2+ concentration ([Ca2+Ii) by glutamate rnetabotropic receptors... more The regulation of intracellular Ca2+ concentration ([Ca2+Ii) by glutamate rnetabotropic receptors (mGluR) was studied in 8-day-old rat forebrain synaptoneurosomes using spectrofluorirnetric methods. Here we demonstrate that metabotropic glutamate agonists induce in rat brain synaptoneurosornes a Ca2+ influx largely dependent upon the presence of Ca2+ in the external medium. The pharmacological profile of this influx is strongly correlated with the pharmacological profile of the activation of phosphoinositide hydrolysis, i.e. quisqualic acid > > 1 S,BR-amino-l-dicarboxylate-l,3 cyclopentane = glutamate. This rnetabotropic glutamate receptor-induced Ca2+ influx is insensitive to voltage-dependent Ca2+ channel antagonists and occurs through a Mn2+ impermeant pathway. The study of the rapid kinetics shows that this influx is triggered after a 300 ms delay compared with that elicited by depolarizing agents and Ca2+ ionophore A23187. In order to assess further if mGluR stimulate this influx through the recruitment of inositol triphosphate (IP3)-sensitive intracellular Ca2+ stores, we have tested the effect of thapsigargin on membrane potential and intracellular Ca2+ simultaneously. Thapsigargin induces a depolarization of the synaptoneurosomal membrane followed by a massive Ca2+ influx, occurring via a Mn2+ nonpermeant route. This depolarizing effect is sensitive to the presence of the intracellular Ca2+ chelator [I ,2-bis(2-aminophenoxy)ethane-N,N,N',~-tetraacetoxymethyl ester], and partially sensitive to extracellular Na+, but insensitive to the presence of extracellular Ca2+. Taken together, our data suggest that mGluR stimulate self-maintained increases of [Ca2+Ii in rat forebrain synaptoneurosornes via the activation of a multistep mechanism, sequenced in the following steps: (i) mGluR-induced IP3 synthesis; (ii) IP3-stimulated intracellular Ca2+ release; (iii) Ca2+-activated non-specific cation channel, leading to local depolarization and a Ca2+ influx; and (iv) activation of Ca2+-sensitive phospholipase C.

Neurochemistry International, Feb 1, 1996

The dependence on Ca 2+ of basal, glutamate-and carbachol-stimulated phosphoinositide (PI) turnov... more The dependence on Ca 2+ of basal, glutamate-and carbachol-stimulated phosphoinositide (PI) turnover was studied on 8-day old rat brain synaptoneurosomes. For that purpose, intracellular and extracellular Ca 2+ concentrations were buffered by bis-(~-aminophenoxy)-ethane-N,N,N',N'-tetraacefic acid, in its tetra(acetoxymethyl)-ester form (BAPTA-AM) and in its free acid form (BAPTA), respectively. The effects of both forms of the calcium chelator intracellular and extracellular Ca 2+ buffering on intracellular and extracellular Ca 2+ concentration ([Ca2+]i and [CaZ+]e) were determined with fluorimetric assay using fura2, either in its acetoxymethyl ester form (fura2-AM) or in its free acid form. Intracellular chelation of Ca 2+ ions with BAPTA-AM induced a dose-dependent reduction of the [Ca2+]~. Basal inositol phosphate (IP) formation was slightly affected by this [CaZ+]~ buffering, while glutamate and carbachol stimulations of PI hydrolysis were similarly diminished. Chelation of extracellular Ca 2+ ions with BAPTA produced a reduction of both [Ca2+]e and [Ca2+]i. Basal IP accumulation was maximally inhibited by 50%. The carbachoMnduced PI hydrolysis was completely inhibited in the presence of 200 #M BAPTA, while a substantial residual glutamate-elicited IP response remained (40% of the control response). It is concluded that [Ca:+]~ of synaptoneurosomes is not critical for basal and neurotransmitter-stimulated IP formation, whilst [Ca2+]e is critical. Glutamate may, in part, stimulate PI breakdown in a Ca2÷-insensitive way. Ca ~'+ play a leading role in a wide variety of neuronal processes such as synaptic placticity (Malenka et al., 1989) and neurotoxicity (Choi, 1988) induced by excitatory amino acids. Intracellular Ca 2÷ concentration ([Ca2+]i) is thus tightly regulated by many systems, including a Na÷/Ca 2÷ exchanger, Ca 2+ ATPases and Ca 2 ÷ binding proteins, in order to avoid uncontrolled loading (Miller, 1991; Pietrobon et al., 1990). Indeed, large unregulated increases in [Ca2+]~ lead to cellular damage by the activation of lyric metabolisms involved in neuronal death (Nicotera et al., 1990). Receptor-mediated phosphoinositide (PI) breakdown, which leads to the formation of two second messengers, e.g. inositol trisphosphate (IP3) and diacylglycerol, is particularly sensitive to [Ca2+]~ changes. In neurons, agents promoting a [Ca2+]~ rise

Neuropharmacology, 1997

The influence of intracellular pH (pHi) changes on the formation of inositol phosphate metabolite... more The influence of intracellular pH (pHi) changes on the formation of inositol phosphate metabolites (IPs) produced by glutamatergic stimulation was studied in g-day-old rat brain synaptoneurosomes. For this purpose pHi was .measured using 2',7'-bis-(2-carboxyl)-5,6-carboxyfluorescein (BCECF) fluorimetric assay in parallel with the basal and receptor-mediated formations of inositol monophosphate (IPl) and inositol bisphosphate (IP2:). We found that glutamate (1 mM), which induces a transient acidification (ApH =-0.05), produces an identical accumulation of IPl and IP2. K+ (30 mM), which provokes an alkalinization of the internal medium (ApH = +0.22), mainly leads to the formation of IPl metabolites. Paired combinations of glutamate with 1,5 and 10 mM NH4+ finally result in an alkalinization of the intrasynaptoneurosomal medium. These combinations produce a strong decrease of the IP2 level concomitant with an increase of the IPl formation, compared to the levels of IPl and IP2 evoked by glutamate alone. The total amount of IPs (IPl+IP2) produced by these combinations is not different from that obtained with glutamate alone. Paired combinations of carbachol with NH4+ produce an identical alkalinization to that produced by NH4+ alone. These combinations produce an increased IPl accumulation, while the IP2 formation is slightly decreased. When the internal medium lis acidified by dimishing the external concentration of Na+, the ratio IPl/IP2 produced after metabotropic glutamate receptor (mGluR) activation is shifted to lower values, while it is not affected for the muscarinic stimulation. These data suggest that the mGluR-associated pathway in synaptoneurosomes is sensitive to pHi shifts, while the muscarinic receptor-associated pathway is less altered when pHi is manipulated. It may be proposed that pH-sensitive inositol phosphate dephosphorylating systems, i.e. phosphatases, are associated with mGluRs in this preparation.

Free Radical Biology Medicine, 2007

Neurochemistry International

Transient peaks of quisqualate (QA)-, but not 1S,3R-l-amino-3-cyclopentane dicarboxylate (1S,3R-A... more Transient peaks of quisqualate (QA)-, but not 1S,3R-l-amino-3-cyclopentane dicarboxylate (1S,3R-ACPD)-and carbachol-induced inositol phosphate formation occur between 2 and 5 days in vitro (DIV) in hippocampal neurons in culture. In order to elucidate the putative origin of such developmental activity differences, the effect of PKC on metabotropic glutamate receptor (mGluR) and musearinic receptor responses was investigated at 3 and 10 DIV. (i) Stimulation of PKC by phorbol-12,13-dibutyrate inhibited QA, 1S,3R-ACPD and carbachol responses at 3 DIV. At 10 DIV, only 1S,3R-ACPD response was still inhibited by phorbol esters. (ii) Inhibition of PKC by staurosporine at 3 DIV potentiated 1S,3R-ACPD-induced inositol phosphate formation, but had no effect on QA and carbachol responses. At 10 DIV, all responses were potentiated by staurosporine. These data strongly suggest that PKC differently modulates 1S,3R-ACPD-and QA-induced inositol phosphate accumulations during in vitro development. The specific activity of mGluRs during development, vs that of muscarinic receptor, and the peculiar modes of regulation by PKC of these two mGluR activities further suggest their particular involvement in the maturation of neuronal culture.

Cellular and Molecular Life Sciences, 2015

HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific re... more HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.