Search

Your search keyword '"Magda Chafai"' showing total 16 results
Start Over Author "Magda Chafai"
16 results on '"Magda Chafai"'

1. Missense mutation of Fmr1 results in impaired AMPAR-mediated plasticity and socio-cognitive deficits in mice

Author

Marta Prieto, Alessandra Folci, Gwénola Poupon, Sara Schiavi, Valeria Buzzelli, Marie Pronot, Urielle François, Paula Pousinha, Norma Lattuada, Sophie Abelanet, Sara Castagnola, Magda Chafai, Anouar Khayachi, Carole Gwizdek, Frédéric Brau, Emmanuel Deval, Maura Francolini, Barbara Bardoni, Yann Humeau, Viviana Trezza, and Stéphane Martin

Subjects
Science
Abstract

The R138Q mutation in the Fragile X Mental Retardation 1 (FMR1) gene has been associated with Fragile X syndrome (FXS). Here, the authors present a Fmr1 R138Q Knock-In mouse model and show that R138Q mutation results in impaired long-term potentiation and socio-cognitive performance in these mice.

Published
2021
Full Text
View/download PDF

2. Sumoylation regulates FMRP-mediated dendritic spine elimination and maturation

Author

Anouar Khayachi, Carole Gwizdek, Gwénola Poupon, Damien Alcor, Magda Chafai, Frédéric Cassé, Thomas Maurin, Marta Prieto, Alessandra Folci, Fabienne De Graeve, Sara Castagnola, Romain Gautier, Lenka Schorova, Céline Loriol, Marie Pronot, Florence Besse, Frédéric Brau, Emmanuel Deval, Barbara Bardoni, and Stéphane Martin

Subjects
Science
Abstract

Fragile X syndrome patients display intellectual disability and autism, caused by mutations in the RNA-binding protein fragile X mental retardation protein (FMRP). Here, the authors show that FMRP sumoylation is required for regulating spine density and maturation.

Published
2018
Full Text
View/download PDF

3. Vasopressin inhibits LTP in the CA2 mouse hippocampal area.

Author

Magda Chafai, Maithé Corbani, Gilles Guillon, and Michel G Desarménien

Subjects
Medicine, Science
Abstract

Growing evidence points to vasopressin (AVP) as a social behavior regulator modulating various memory processes and involved in pathologies such as mood disorders, anxiety and depression. Accordingly, AVP antagonists are actually envisaged as putative treatments. However, the underlying mechanisms are poorly characterized, in particular the influence of AVP on cellular or synaptic activities in limbic brain areas involved in social behavior. In the present study, we investigated AVP action on the synapse between the entorhinal cortex and CA2 hippocampal pyramidal neurons, by using both field potential and whole-cell recordings in mice brain acute slices. Short application (1 min) of AVP transiently reduced the synaptic response, only following induction of long-term potentiation (LTP) by high frequency stimulation (HFS) of afferent fibers. The basal synaptic response, measured in the absence of HFS, was not affected. The Schaffer collateral-CA1 synapse was not affected by AVP, even after LTP, while the Schaffer collateral-CA2 synapse was inhibited. Although investigated only recently, this CA2 hippocampal area appears to have a distinctive circuitry and a peculiar role in controlling episodic memory. Accordingly, AVP action on LTP-increased synaptic responses in this limbic structure may contribute to the role of this neuropeptide in controlling memory and social behavior.

Published
2012
Full Text
View/download PDF

4. Author response for 'Influenza vaccination and prognosis of COVID ‐19 in hospitalized patients with diabetes: Results from the CORONADO study'

Author

null A Diallo, null M Pichelin, null M Wargny, null P Gourdy, null JB Bonnet, null S Hadjadj, null B Cariou, null A Sultan, null F Galtier, null Matthieu Wargny, null Pascale Mahot, null Bertrand Cariou, null Samy Hadjadj, null Matthieu Pichelin, null Anne‐Laure Fournier‐Guilloux, null Nicolas Mauduit, null Edith Bigot‐Corbel, null Anne‐Sophie Boureau, null Laure Dekcer, null Audrey Ernould, null Claire Primot, null Anne Seguin, null Marielle Joliveau, null Sonia Pouvreau, null Chloé FOURNIER, null Jeremy Thureau, null Edith Fonteneau, null Pamela Hublain, null Chu Nantes, null Carole Agasse, null Mathilde DE Kergaradec, null Vincent Minville, null Fanny Vardon‐Bounes, null Guillaume Martin‐Blondel, null Pierre Gourdy, null Blandine Tramunt, null Marie‐Christine Turnin, null Hélène Hanaire, null Jean‐Michel Mansuy, null Didier Fabre, null Marie‐Blanche Arhainx, null Laurent Cazals, null Laure Combes, null Emmanuelle Lami, null Mallory Cianferani, null Bruno Megarbane, null Pierre Leroy, null Jean‐François Gautier, null Tiphaine Vidal‐Trecan, null Jean‐Pierre Riveline, null Jean‐Louis Laplanche, null Stéphane Mouly, null Louis Potier, null Ronan Roussel, null Malak Taher, null Yawa Abouleka, null Fetta Yaker, null Aurelie Carlier, null Anne Boutten, null Marilyne Hallot‐Feron, null Fadila Mourah, null Charles Thivolet, null Emilie Blond, null Muriel Rolland, null Josep Verdecho Mendez, null Marine Alexandre, null Julien Pottecher, null Emilie Richer, null Laurent Meyer, null Florina Luca, null Jean‐Marc Lessinger, null Thibault Bahougne, null Bruno Guerci, null Lisa Ludwig, null Siham Benzirar, null Catherine Malaplate, null Thierry Matton, null Julien Poissy, null Karine Faure, null Pierre Fontaine, null Florence Baudoux, null Anne Vambergue, null Jean David Pekar, null Marc Lambert, null Cécile Yelnik, null Amélie Bruandet, null Laurent Petit, null Didier Neau, null Vincent Rigalleau, null Annie Berard, null Amandine Galioot, null Remy Coudroy, null Arnaud Thille, null René Robert, null France Roblot‐Cazenave, null Blandine Rammaert, null Pierre Jean Saulnier, null Xavier Piguel, null Nesrine Benhenda, null Camille Husson, null Celine Olivier, null Florence Torremocha, null Mathilde Fraty, null Marie Flamen d'assigny, null Aurelie Miot, null Valentin Bossard, null Kada Klouche, null Alain Makinson, null Ariane Sultan, null Jean‐Baptiste Bonnet, null Vincent Foulongne, null Florence Galtier, null Cécile Aubron, null Séverine Ansart, null Véronique Kerlan, null Pascale Quiniou, null Jean‐Luc Carre, null Stéphane Quesnot, null Bruno Laviolle, null Carole Schwebel, null Olivier Epaulard, null Pierre‐Yves Benhamou, null Cécile Betry, null Anne‐Laure Borel, null Sandrine Lablanche, null Dorra Guergour, null Catherine Duclos, null Emmanuel Cosson, null Erwan Guyot, null Aurore Deniau, null Phucthutrang Nguyen, null Yves Reznik, null Michael Joubert, null Stéphane Allouche, null Lydia Guittet, null Steven Grange, null Manuel Etienne, null Gaëtan Prévost, null Valéry Brunel, null Jean‐Christophe Lagier, null Didier Raoult, null Anne Dutour, null Bénédicte Gaborit, null Sandrine Boulllu, null Patrice Darmon, null Adèle Lasbleiz, null Mathieu Cerino, null Fanny Romain, null Marie Houssays, null Jean Pierre Quenot, null Lionel Piroth, null Bruno Vergès, null Laurence Duvillard, null Bernard Bonnotte, null Alain Mercat, null Vincent Dubee, null Ingrid Allix, null Patrice Rodien, null Robin Dhersin, null Maylis Lebeault, null Wojciech Trzepizur, null Jocelyne Loison, null Antoine Brangier, null Pierre Asfar, null Pascal Reynier, null Françoise Larcher, null Françoise Joubaud, null Marie‐Rita Andreu, null Geoffrey Urbanski, null Laurent Hubert, null Cedric Annweiler, null Jean Dellamonica, null Johan Courjon, null Nicolas Chevalier, null Giulia Chinetti, null Magda Chafai, null Bruno Mourvillier, null Firouze Bani‐Sadr, null Sarra Barraud, null Brigitte Delemer, null Philippe Gillery, null Pascale Labedade, null Amélie Chabrol, null Alfred Penfornis, null Catherine Petit, null Coralie Amadou, null Maxime Adler, null Clément Dubost, null Pierre‐Louis Conan, null Lyse Bordier, null Franck Ceppa, null Cyril Garcia, null Mathilde Sollier, null Olivier Dupuy, null Sophie Laplance, null Olivier Billuart, null Marie Joseph Aroulanda, null Frédérique Olivier, null Florence Ayon, null Nathalie Wilhelm, null Loic Epelboin, null Nadia Sabbah, null Aurelie Charpin, null Pierre Squara, null Olivier Belliard, null Claude Dubois, null Michel Marre, null Johann Auchabie, null Roxane Courtois, null Thierry Duriez, null Tiphaine Mergey, null Laura Vallee, null Laetitia Seguin, null Abdallah Al‐Salameh, null Jean‐Philippe Lanoix, null Sandrine Soriot‐Thomas, null Anne‐Marie Bourgeois‐Descouls, null Rachel Desailloud, null Natacha Germain, null Bogdan Galusca, null Gwenaelle Belleton, null Nesrine Marouani, null Delia Palaghiu, null Amira Hammour, null Fernando Berdaguer, null Thimothée Klopfenstein, null Hajer Zayet, null Patrice Winiszewski, null Marie Zanusso, null Pauline Garnier, null Ingrid Julier, null Karim Hamzaoui, null Sophie Marty‐Gres, null Tarik Sadki, null Lucile Cadot, null Jean‐Louis Dubost, null Céline Gonfroy, null Catherine Campinos, null Pascale Martres, null Marie Pierre Coulhon, null Nicolas Allou, null Marwa Bachir, null Stella Hoang, null Candice Kembellec, null Olivia Suply, null Fatima Kharcha, null Anne‐Claire Devouge, null Anna Flaus‐Furmanuk, null Isabelle Madeline, null Vincent Ehinger, null Sophie Bastard, null Loic Raffray, null Frederic Renou, null Aude Bojarski, null Caroline Paul, null Karine Borsu, null Angelique Gorlin, null Servane Bernardo, null Carole Truong Ut, null Stephane Renaud, null Antoine Vignoles, null Emilie Foch, null Laurie Masse, null Hubert Grand, null Helene Ferrand, null Christelle Raffaitin‐Cardin, null Hadjer Zellagui, null Celine Castang‐Brachet, null Frederique Boury, null Ana Alvarez Tena, null Isabelle Moura, null Pierre Kalfon, null Juliana Darasteanu, null Arnaud Monier, null Pascal Foucault, null Alexandra Depuille, null Stéphanie Laugier‐Robiolle, null Patrick Caneiro, null Maud Basso, null Etienne Larger, null Samir Bouam, null Wahiba Benzenati, null Leila Ait Bachir, null Camille Cussac Pillegand, null Marc Vasse, null Christophe Michard, null Nathanaëlle Montanier, null Luc Millot, null Françoise Crepet, null Danielle Ratsimba, null Kevin Bouiller, null Sophie Borot, null Isabelle Bruckert, null Annie Clergeot, null Franck Schillo, null Dorothée Vignes, null Muriel Bourgeon‐Ghittori, null Hamoud Lachgar, null Claire Lambert DE Cursay, null Stéphane Levante, null Jean Charles Auregan, null Antoine Merlet, null Cécile Zaragoza, null Gwénaëlle Arnault, null Anne‐Gaëlle Loupp, null Olivier Lesieur, null Mariam Roncato‐Saberan, null Didier Gouet, null Romain Lemarie, null Hong_an Allano, null Emmanuel Vivier, null Caroline Pariset, null Cédric Luyton, null Lucien Marchand, null Fanny Doroszewski, null Matthieu Pecquet, null Laurent Perard, null Sylvie Vuillermoz‐Blas, null Nicolas Kacki, null Patricia Charrier, null Amélie Ducet‐Boiffard, null Françoise Desroys Roure, null Olivier Bourron, null Dominique Bonnefont‐Rousselot, null Suzanne Laroche, null Franck Phan, null Agnès Hartemann, null Cyrielle Caussy, null Emmanuel Disse, null Claude Guerin, null Thomas Perpoint, null Philippe Moulin, null Régine Cartier, null Geoffroy Hariri, null Dorothée Chopin, null Camille Vatier, null Nathalie Bourcigaux, null Emmanuelle Chaigneau, null Sophie Christin‐Maitre, null Bruno Donadille, null Bruno Feve, null Sophie Lamothe, null Julie Sarfati, null Pascal Pernet, null Anne Chambon, null Delphine Demarsy, null Hugo Campagne, null Françoise Latil‐Plat, null Monica Berne, null Marilyne Grinand, null Marion Touzet, null Aydrey Zabulon, null Jocelyne Craspag, null Catherine Ledoux, null Cedric Contaret, null Blandine Janand‐Delenne, null Anaïs Giraud, null Marie Lou Lacrimini, null Joëlle Arrivie, null Deborah Ancelle, null Carine Guillois, null Bénédicte Fremy, null Amina Chaalal, null Gaëlle Barrande, null Anne Dorange, null Eglantine Rouanet, null Dominique Seret‐Begue, null Audrey Saoud, null Anne‐Marie Guedj, null Nathalie Bedos, null Fritz‐Line Velayoudom, null Marie Dumas, null Benoite Gonda, null Christine Coffin, null Stéphanie Gibiat, null Myriam Lungo, null Chantal Bully, null Pierre Serusclat, null Stella Bully, null Patricia Carre, null Jean‐Philippe Leberre, null Carlos Elkhoury, null Marine Thieux, null Laetitia Paradisi‐Prieur, and null CORONADO investigators

Subjects
Vaccination, Pediatrics, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, Hospitalized patients, Diabetes mellitus, Medicine, business, medicine.disease
Published
2021

5. Involvement of ASIC1a channels in the spinal processing of pain information by deep projection neurons

Author

Kevin Delanoe, Eric Lingueglia, Romain Veltz, Ludivine Pidoux, Ariane Delrocq, Perrine Inquimbert, Emmanuel Deval, Magda Chafai, Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)

Subjects
0303 health sciences, [SDV]Life Sciences [q-bio], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Chronic pain, Iberiotoxin, medicine.disease, Apamin, Spinal cord, Inhibitory postsynaptic potential, Potassium channel, 03 medical and health sciences, chemistry.chemical_compound, Electrophysiology, 0302 clinical medicine, medicine.anatomical_structure, chemistry, Neuroplasticity, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, medicine, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neuroscience, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract

Dorsal horn of the spinal cord is an important crossroad of pain neuraxis, especially for the neuronal plasticity mechanisms that can lead to chronic pain states. Windup is a well-known spinal pain facilitation process initially described several decades ago, but which exact mechanism is still not fully understood. Here, we combine bothex vivoandin vivoelectrophysiological recordings of spinal neurons with computational modelling to demonstrate a role for ASIC1a-containing channels in the windup process. Spinal application of the ASIC1a inhibitory venom peptides mambalgin-1 and psalmotoxin-1 (PcTx1) significantly reduces the ability of deep wide dynamic range (WDR) neurons to develop windupin vivo. All deep WDR-like neurons recorded from spinal slices exhibit an ASIC current with biophysical and pharmacological characteristics consistent with functional expression of ASIC1a/ASIC2 heteromeric channels. A computational model of WDR neuron supplemented with heteromeric ASIC1a/ASIC2 channel parameters accurately reproduces the experimental data, further supporting a positive contribution of these channels to windup. It also predicts a calcium-dependent windup decrease for elevated ASIC conductances, a phenomenon that was experimentally validated using either a combination of calcium-activated potassium channel inhibitory peptides (apamin and iberiotoxin), or the Texas coral snake ASIC-activating toxin (MitTx). This study demonstrates a possible dual contribution to windup of calcium permeable ASIC1a/ASIC2 channels in deep laminae projecting neurons, promoting it upon moderate channel activity, but ultimately leading to calcium-dependent windup inhibition associated to potassium channels when activity increases.

Published
2021

6. Missense mutation of Fmr1 results in impaired AMPAR-mediated plasticity and socio-cognitive deficits in mice

Author

Gwénola Poupon, Sara Castagnola, Sara Schiavi, Marta Prieto, Alessandra Folci, Viviana Trezza, Frédéric Brau, Emmanuel Deval, Sophie Abelanet, Carole Gwizdek, Marie Pronot, Stéphane Martin, Urielle François, Anouar Khayachi, Barbara Bardoni, Yann Humeau, Paula A. Pousinha, N. Lattuada, Maura Francolini, Magda Chafai, Valeria Buzzelli, Prieto, M., Folci, A., Poupon, G., Schiavi, S., Buzzelli, V., Pronot, M., Francois, U., Pousinha, P., Lattuada, N., Abelanet, S., Castagnola, S., Chafai, M., Khayachi, A., Gwizdek, C., Brau, F., Deval, E., Francolini, M., Bardoni, B., Humeau, Y., Trezza, V., Martin, S., Martin, Stephane, Explorer des stratégies innovantes pour restaurer la fonction synaptique et les comportements sociocognitifs dans un modèle murin exprimant une mutation récurrente du syndrome du X fragile chez l'humain - - InnoVinFXS2020 - ANR-20-CE16-0006 - AAPG2020 - VALID, Idex UCA JEDI - - UCA JEDI2015 - ANR-15-IDEX-0001 - IDEX - VALID, Centres d'excellences - Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie - - SIGNALIFE2011 - ANR-11-LABX-0028 - LABX - VALID, Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Università degli Studi Roma Tre = Roma Tre University (ROMA TRE), Interdisciplinary Institute for Neuroscience [Bordeaux] (IINS), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Milano = University of Milan (UNIMI), ANR-20-CE16-0006,InnoVinFXS,Explorer des stratégies innovantes pour restaurer la fonction synaptique et les comportements sociocognitifs dans un modèle murin exprimant une mutation récurrente du syndrome du X fragile chez l'humain(2020), ANR-15-IDEX-0001,UCA JEDI,Idex UCA JEDI(2015), ANR-11-LABX-0028,SIGNALIFE,Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie(2011), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Università degli Studi Roma Tre, Università degli Studi di Milano [Milano] (UNIMI), and ANR-15-IDEX-01

Subjects
0301 basic medicine, Male, Patch-Clamp Techniques, [SDV]Life Sciences [q-bio], Long-Term Potentiation, General Physics and Astronomy, Hippocampus, Membrane trafficking, medicine.disease_cause, Fragile X Mental Retardation Protein, Mice, 0302 clinical medicine, Missense mutation, Cells, Cultured, Mutation, Multidisciplinary, Brain, Long-term potentiation, Autism spectrum disorders, Fragile X syndrome, [SDV] Life Sciences [q-bio], Mechanisms of disease, Receptors, Glutamate, Female, congenital, hereditary, and neonatal diseases and abnormalities, Science, Immunoblotting, Mutation, Missense, AMPA receptor, Biology, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, medicine, Animals, Humans, Biotinylation, Cognitive Dysfunction, Protein transport, General Chemistry, medicine.disease, FMR1, nervous system diseases, 030104 developmental biology, Autism, Neuroscience, 030217 neurology & neurosurgery
Abstract

Fragile X syndrome (FXS) is the most frequent form of inherited intellectual disability and the best-described monogenic cause of autism. CGG-repeat expansion in the FMR1 gene leads to FMR1 silencing, loss-of-expression of the Fragile X Mental Retardation Protein (FMRP), and is a common cause of FXS. Missense mutations in the FMR1 gene were also identified in FXS patients, including the recurrent FMRP-R138Q mutation. To investigate the mechanisms underlying FXS caused by this mutation, we generated a knock-in mouse model (Fmr1R138Q) expressing the FMRP-R138Q protein. We demonstrate that, in the hippocampus of the Fmr1R138Q mice, neurons show an increased spine density associated with synaptic ultrastructural defects and increased AMPA receptor-surface expression. Combining biochemical assays, high-resolution imaging, electrophysiological recordings, and behavioural testing, we also show that the R138Q mutation results in impaired hippocampal long-term potentiation and socio-cognitive deficits in mice. These findings reveal the functional impact of the FMRP-R138Q mutation in a mouse model of FXS., The R138Q mutation in the Fragile X Mental Retardation 1 (FMR1) gene has been associated with Fragile X syndrome (FXS). Here, the authors present a Fmr1R138Q Knock-In mouse model and show that R138Q mutation results in impaired long-term potentiation and socio-cognitive performance in these mice.

Published
2021

7. Abnormal AMPAR-mediated synaptic plasticity, cognitive and autistic-like behaviors in a missense Fmr1 mutant mouse model of Fragile X syndrome

Author

Marta Prieto, Alessandra Folci, Gwénola Poupon, Sara Schiavi, Valeria Buzzelli, Marie Pronot, Urielle François, Paula Pousinha, Norma Lattuada, Sophie Abelanet, Sara Castagnola, Magda Chafai, Anouar Khayachi, Carole Gwizdek, Frédéric Brau, Emmanuel Deval, Maura Francolini, Barbara Bardoni, Yann Humeau, Viviana Trezza, Stéphane Martin, Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)

Subjects
0303 health sciences, Mutation, congenital, hereditary, and neonatal diseases and abnormalities, [SDV]Life Sciences [q-bio], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Long-term potentiation, AMPA receptor, Biology, medicine.disease, medicine.disease_cause, FMR1, nervous system diseases, Fragile X syndrome, 03 medical and health sciences, 0302 clinical medicine, Postsynaptic potential, Synaptic plasticity, medicine, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Missense mutation, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neuroscience, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract

Fragile X syndrome (FXS) is the most frequent form of inherited intellectual disability and the best-described monogenic cause of autism. FXS is usually caused by a CGG-repeat expansion in the FMR1 gene leading to its silencing and the loss-of-expression of the Fragile X Mental Retardation Protein (FMRP). Missense mutations were also identified in FXS patients, including the recurrent FMRP-R138Q mutation. To investigate the mechanisms underlying FXS in these patients, we generated a knock-in mouse model (Fmr1R138Q) expressing the FMRP-R138Q protein. We demonstrate that the Fmr1R138Q hippocampus has an increased spine density associated with postsynaptic ultrastructural defects and increased AMPA receptor surface expression. Combining biochemical assays, high-resolution imaging and electrophysiological recordings, we also show that the mutation impairs the hippocampal long-term potentiation (LTP) and leads to socio-cognitive deficits in Fmr1R138Q mice. These findings reveal that the R138Q mutation impacts the synaptic functions of FMRP and highlight potential mechanisms causing FXS in FMRP-R138Q patients.

Published
2020

8. Neuroanatomical distribution and function of the vasopressin V1B receptor in the rat brain deciphered using specific fluorescent ligands

Author

Maithé Corbani, Michel G. Desarménien, Rafik Marir, Magda Chafai, Aleksandra Olma, Gilles Guillon, Csaba Tömböly, Anne Vincent, Amélie M. Borie, Yoichi Ueta, Miguel Trueba, Maurice Manning, Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Occupational and Environmental Health [Kitakyushu] (UEOH), Department of Biochemistry and Cancer Biology, and University of Toledo

Subjects
0301 basic medicine, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Central nervous system, Hippocampus, Anxiety, Biology, Stress, Rodents, 03 medical and health sciences, Glutamatergic, GPCR, 0302 clinical medicine, Endocrinology, Vasopressin receptors, Internal medicine, medicine, Receptor, G protein-coupled receptor, Vasopressin receptor, Arginine vasopressin receptor 1B, 030104 developmental biology, medicine.anatomical_structure, V(1B) brain anatomy, GABAergic, Animal Science and Zoology, Neuroscience, 030217 neurology & neurosurgery
Abstract

International audience; It is now accepted that vasopressin, through V1A/V1B receptors, centrally regulates cognitive functions such as memory, affiliation, stress, fear and depression. However, the respective roles of these receptor isoforms and their contribution to stress-related pathologies remain uncertain. The development of new therapeutic treatments requires a precise knowledge of the distribution of these receptors within the brain, which has been so far hampered by the lack of selective V1B markers. In the present study, we have determined the pharmacological properties of three new potent rat V1B fluorescent ligands and demonstrated that they constitute valuable tools for simultaneous visualization and activation of native V1B receptors in living rat brain tissue. Thus, d[Leu4,Lys-Alexa 647)8]VP (analogue 3), the compound with the best affinity-selectivity/fluorescence ratio for the V1B receptor emerged as the most promising. The rat brain regions most concerned by stress such as hippocampus, olfactory bulbs, cortex and amygdala display the highest V1B fluorescent labelling with analogue 3. In the hippocampus CA2, V1B receptors are located on glutamatergic, not GABAergic neurones, and are absent from astrocytes. Using AVP-EGFP rats, we demonstrate the presence of V1B autoreceptors on AVP-secreting neurones not only in the hypothalamus, but also sparsely in the hippocampus. Finally, using both electrophysiology and visualization of ERK phosphorylation, we show analogue 3-induced activation of the V1B receptor in situ. This will help to analyse expression and functionality of V1B receptors in the brain and contribute to further explore the AVPergic circuitry in normal and pathological conditions.

Published
2018

9. η-Secretase processing of APP inhibits neuronal activity in the hippocampus

Author

Scherazad Kootar, Marc Aurel Busche, Steven Moore, Lewis D. B. Evans, Sabina Tahirovic, Daniel Hornburg, Dietmar Rudolf Thal, Anna Daria, Hélène Marie, Jochen Herms, Frederick J. Livesey, Christian Haass, Elisabeth Kremmer, Vilmantas Giedraitis, Felix Meissner, Heike Hampel, Veronika Müller, Ulrike Müller, Michael Willem, Camilla Giudici, Saak V. Ovsepian, Michael T. Heneka, Brigitte Nuscher, Lars Lannfelt, Andrea Wenninger-Weinzierl, Arthur Konnerth, Magda Chafai, Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Equipe de Recherche en Syntaxe et Sémantique (ERSS), Université Toulouse - Jean Jaurès (UT2J)-Université Bordeaux Montaigne-Centre National de la Recherche Scientifique (CNRS), European IPF Registry and Biobank (eurIPFreg/bank), Institut für Molekulare Immunologie, GSF, German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Department of Public health and Caring Sciences, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden, Department of Experimental Systems Immunology [Martinsried, Allemagne], Max Planck Institute of Biochemistry (MPIB), Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Ludwig-Maximilians-Universität München (LMU), Institute of Neuroscience and Center for Integrated Protein Science, and Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)

Subjects
enzymology [Neurites], Male, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, ADAM10, Long-Term Potentiation, physiology [Hippocampus], genetics [Amyloid Precursor Protein Secretases], Plaque, Amyloid, antagonists & inhibitors [Amyloid Precursor Protein Secretases], Molecular neuroscience, Hippocampal formation, Hippocampus, APP protein, human, ADAM10 Protein, Mice, Amyloid beta-Protein Precursor, 0302 clinical medicine, metabolism [Amyloid beta-Protein Precursor], metabolism [Peptide Fragments], Aspartic Acid Endopeptidases, Premovement neuronal activity, chemistry [Amyloid beta-Protein Precursor], ComputingMilieux_MISCELLANEOUS, Neurons, enzymology [Neurons], 0303 health sciences, Multidisciplinary, biology, metabolism [Neurites], Long-term potentiation, deficiency [Amyloid Precursor Protein Secretases], antagonists & inhibitors [Aspartic Acid Endopeptidases], metabolism [Aspartic Acid Endopeptidases], physiology [Neurons], Research Highlight, cerebrospinal fluid [Amyloid beta-Protein Precursor], Ectodomain, Biochemistry, genetics [Amyloid beta-Protein Precursor], Female, ddc:500, Single-Cell Analysis, metabolism [Alzheimer Disease], metabolism [Matrix Metalloproteinases, Membrane-Associated], Matrix Metalloproteinases, Membrane-Associated, Bace1 protein, mouse, ADAM10 protein, human, In Vitro Techniques, Article, 03 medical and health sciences, enzymology [Hippocampus], Calcium imaging, cerebrospinal fluid [Amyloid Precursor Protein Secretases], Alzheimer Disease, BACE1 protein, human, mental disorders, deficiency [Matrix Metalloproteinases, Membrane-Associated], Neurites, Animals, Humans, Calcium Signaling, deficiency [Aspartic Acid Endopeptidases], Mmp24 protein, mouse, 030304 developmental biology, enzymology [Alzheimer Disease], Membrane Proteins, metabolism [Amyloid Precursor Protein Secretases], Peptide Fragments, Molecular Weight, ADAM Proteins, Disease Models, Animal, genetics [Aspartic Acid Endopeptidases], metabolism [ADAM Proteins], cytology [Hippocampus], chemistry [Peptide Fragments], Proteolysis, biology.protein, Amyloid Precursor Protein Secretases, Protein Processing, Post-Translational, Amyloid precursor protein secretase, metabolism [Membrane Proteins], 030217 neurology & neurosurgery
Abstract

Alzheimer's disease (AD) is characterized by the accumulation of amyloid plaques, which are predominantly composed of amyloid β-peptide (Aβ)1. Two principal physiological pathways either prevent or promote Aβ generation from its precursor (amyloid precursor protein; APP) in a competitive manner1. Modulation of the amyloidogenic pathway is currently exploited by anti-Aβ therapeutic strategies2. Although APP processing has been studied in great detail, unknown proteolytic events appear to hinder stoichiometric analyses of APP metabolism in vivo3. We now identified higher molecular weight C-terminal fragments of APP (CTF-η) in addition to the long-known α- and β-secretase (a disintegrin and metalloproteinase; ADAM10 and β-site APP cleaving enzyme 1; BACE1) generated CTF-α and CTF-β. Generation of CTF-η is mediated in part by membrane bound matrix-metalloproteinases such as MT5-MMP, referred to as η-secretase activity. η-Secretase cleavage occurs primarily at amino acids 504/505 of APP(695) releasing a truncated, soluble APP ectodomain (sAPP-η). Upon shedding of sAPP-η CTF-η is further processed by ADAM10 and BACE1 to release long and short Aη peptides (Aη-α and Aη-β). Aη peptides are therefore distinct from N-terminally extended Aβ variants4,5, since they do not extend to the γ-secretase cleavage sites. η-Secretase produced CTFs are enriched in dystrophic neurites in an AD mouse model and human AD brains6. Genetic and pharmacological inhibition of BACE1 activity results in a robust accumulation of CTF-η and Aη-α. In mice treated with a potent BACE1 inhibitor hippocampal long-term potentiation (LTP) was reduced. Strikingly, when recombinant or synthetic Aη-α was applied on hippocampal slices ex vivo, LTP was lowered. Furthermore, in vivo single cell two-photon calcium imaging revealed that hippocampal neuronal activity was attenuated by Aη-α. These findings not only demonstrate a major physiologically relevant APP processing pathway but may also suggest potential translational relevance for therapeutic strategies targeting APP processing.

Published
2015

10. Subchronic Glucocorticoid Receptor Inhibition Rescues Early Episodic Memory and Synaptic Plasticity Deficits in a Mouse Model of Alzheimer’s Disease

Author

Magda Chafai, Ana Rita Salgueiro Pereira, Xavier Mouska, Hélène Marie, Ingrid Bethus, Fabien Lanté, Elisabeth F. Raymond, Scherazad Kootar, and Jacques Barik

Subjects
medicine.medical_specialty, Memory, Episodic, Hippocampus, Mice, Transgenic, Dexamethasone, Amyloid beta-Protein Precursor, Mice, Hormone Antagonists, Receptors, Glucocorticoid, Glucocorticoid receptor, Alzheimer Disease, Quinoxalines, Internal medicine, medicine, Animals, Humans, Glucocorticoids, Episodic memory, Pharmacology, Memory Disorders, Neuronal Plasticity, Excitatory Postsynaptic Potentials, Recognition, Psychology, Valine, Long-term potentiation, medicine.disease, Mice, Inbred C57BL, Disease Models, Animal, Mifepristone, Psychiatry and Mental health, Endocrinology, Mutation, Synaptic plasticity, NMDA receptor, Original Article, Alzheimer's disease, Psychology, Excitatory Amino Acid Antagonists, Neuroscience, Glucocorticoid, medicine.drug
Abstract

The early phase of Alzheimer's disease (AD) is characterized by hippocampus-dependent memory deficits and impaired synaptic plasticity. Increasing evidence suggests that stress and dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis, marked by the elevated circulating glucocorticoids, are risk factors for AD onset. How these changes contribute to early hippocampal dysfunction remains unclear. Using an elaborated version of the object recognition task, we carefully monitored alterations in key components of episodic memory, the first type of memory altered in AD patients, in early symptomatic Tg2576 AD mice. We also combined biochemical and ex vivo electrophysiological analyses to reveal novel cellular and molecular dysregulations underpinning the onset of the pathology. We show that HPA axis, circadian rhythm, and feedback mechanisms, as well as episodic memory, are compromised in this early symptomatic phase, reminiscent of human AD pathology. The cognitive decline could be rescued by subchronic in vivo treatment with RU486, a glucocorticoid receptor antagonist. These observed phenotypes were paralleled by a specific enhancement of N-Methyl-D-aspartic acid receptor (NMDAR)-dependent LTD in CA1 pyramidal neurons, whereas LTP and metabotropic glutamate receptor-dependent LTD remain unchanged. NMDAR transmission was also enhanced. Finally, we show that, as for the behavioral deficit, RU486 treatment rescues this abnormal synaptic phenotype. These preclinical results define glucocorticoid signaling as a contributing factor to both episodic memory loss and early synaptic failure in this AD mouse model, and suggest that glucocorticoid receptor targeting strategies could be beneficial to delay AD onset.

Published
2015

11. Neuroanatomical distribution and function of the vasopressin V

Author

Maithé, Corbani, Rafik, Marir, Miguel, Trueba, Magda, Chafai, Anne, Vincent, Amélie M, Borie, Michel G, Desarménien, Yoichi, Ueta, Csaba, Tomboly, Aleksandra, Olma, Maurice, Manning, and Gilles, Guillon

Subjects
Male, Neurons, Receptors, Vasopressin, Staining and Labeling, Vasopressins, Hypothalamus, Brain, CHO Cells, Ligands, Arginine Vasopressin, Rats, Sprague-Dawley, Neuroanatomy, Cricetulus, HEK293 Cells, Receptors, GABA, Astrocytes, Cricetinae, Pituitary Gland, Animals, Humans, Fluorescent Dyes
Abstract

It is now accepted that vasopressin, through V

Published
2017

12. Dual contribution of ASIC1a channels in the spinal processing of pain information by deep projection neurons revealed by computational modeling.

Author

Magda Chafaï, Ariane Delrocq, Perrine Inquimbert, Ludivine Pidoux, Kevin Delanoe, Maurizio Toft, Frederic Brau, Eric Lingueglia, Romain Veltz, and Emmanuel Deval

Subjects
Biology (General), QH301-705.5
Abstract

Dorsal horn of the spinal cord is an important crossroad of pain neuraxis, especially for the neuronal plasticity mechanisms that can lead to chronic pain states. Windup is a well-known spinal pain facilitation process initially described several decades ago, but its exact mechanism is still not fully understood. Here, we combine both ex vivo and in vivo electrophysiological recordings of rat spinal neurons with computational modeling to demonstrate a role for ASIC1a-containing channels in the windup process. Spinal application of the ASIC1a inhibitory venom peptides mambalgin-1 and psalmotoxin-1 (PcTx1) significantly reduces the ability of deep wide dynamic range (WDR) neurons to develop windup in vivo. All deep WDR-like neurons recorded from spinal slices exhibit an ASIC current with biophysical and pharmacological characteristics consistent with functional expression of ASIC1a homomeric channels. A computational model of WDR neuron supplemented with different ASIC1a channel parameters accurately reproduces the experimental data, further supporting a positive contribution of these channels to windup. It also predicts a calcium-dependent windup decrease for elevated ASIC conductances, a phenomenon that was experimentally validated using the Texas coral snake ASIC-activating toxin (MitTx) and calcium-activated potassium channel inhibitory peptides (apamin and iberiotoxin). This study supports a dual contribution to windup of calcium permeable ASIC1a channels in deep laminae projecting neurons, promoting it upon moderate channel activity, but ultimately leading to calcium-dependent windup inhibition associated to potassium channels when activity increases.

Published
2023
Full Text
View/download PDF

13. mGlu5 receptors regulate synaptic sumoylation via a transient PKC-dependent diffusional trapping of Ubc9 into spines

Author

Frédéric Cassé, Anouar Khayachi, Emmanuel Deval, Gwénola Poupon, Céline Loriol, Carole Gwizdek, Magda Chafai, Stéphane Martin, Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)

Subjects
Receptor, Metabotropic Glutamate 5, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV]Life Sciences [q-bio], SUMO protein, General Physics and Astronomy, Neurotransmission, Hippocampus, Synaptic Transmission, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Mice, 0302 clinical medicine, Animals, Protein kinase C, Cells, Cultured, Protein Kinase C, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Neurons, 0303 health sciences, Multidisciplinary, biology, GABAA receptor, Chemistry, Sumoylation, General Chemistry, Sumoylation Pathway, Hedgehog signaling pathway, Cell biology, Gq alpha subunit, Synapses, Ubiquitin-Conjugating Enzymes, biology.protein, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Phosphorylation, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 030217 neurology & neurosurgery
Abstract

Sumoylation plays important roles in the modulation of protein function, neurotransmission and plasticity, but the mechanisms regulating this post-translational system in neurons remain largely unknown. Here we demonstrate that the synaptic diffusion of Ubc9, the sole conjugating enzyme of the sumoylation pathway, is regulated by synaptic activity. We use restricted photobleaching/photoconversion of individual hippocampal spines to measure the diffusion properties of Ubc9 and show that it is regulated through an mGlu5R-dependent signalling pathway. Increasing synaptic activity with a GABAA receptor antagonist or directly activating mGlu5R increases the synaptic residency time of Ubc9 via a Gαq/PLC/Ca(2+)/PKC cascade. This activation promotes a transient synaptic trapping of Ubc9 through a PKC phosphorylation-dependent increase of Ubc9 recognition to phosphorylated substrates and consequently leads to the modulation of synaptic sumoylation. Our data demonstrate that Ubc9 diffusion is subject to activity-dependent regulatory processes and provide a mechanism for the dynamic changes in sumoylation occurring during synaptic transmission.

Published
2014

14. Vasopressin Inhibits LTP in the CA2 Mouse Hippocampal Area

Author

Gilles Guillon, Michel G. Desarménien, Magda Chafai, and Maithé Corbani

Subjects
Male, Vasopressin, Anatomy and Physiology, Patch-Clamp Techniques, Mouse, Vasopressins, Long-Term Potentiation, CA2 Region, Hippocampal, Hippocampus, lcsh:Medicine, Hippocampal formation, Neurotransmission, Biochemistry, Synaptic Transmission, Neurological System, Synapse, Mice, Model Organisms, Animals, lcsh:Science, Biology, Multidisciplinary, Neuromodulation, Pyramidal Cells, lcsh:R, Excitatory Postsynaptic Potentials, Long-term potentiation, Neurochemistry, Animal Models, Neuroendocrinology, Entorhinal cortex, Electric Stimulation, Mice, Inbred C57BL, nervous system, Anesthesia, Cellular Neuroscience, Synapses, Excitatory postsynaptic potential, lcsh:Q, Neuroscience, hormones, hormone substitutes, and hormone antagonists, Research Article
Abstract

Growing evidence points to vasopressin (AVP) as a social behavior regulator modulating various memory processes and involved in pathologies such as mood disorders, anxiety and depression. Accordingly, AVP antagonists are actually envisaged as putative treatments. However, the underlying mechanisms are poorly characterized, in particular the influence of AVP on cellular or synaptic activities in limbic brain areas involved in social behavior. In the present study, we investigated AVP action on the synapse between the entorhinal cortex and CA2 hippocampal pyramidal neurons, by using both field potential and whole-cell recordings in mice brain acute slices. Short application (1 min) of AVP transiently reduced the synaptic response, only following induction of long-term potentiation (LTP) by high frequency stimulation (HFS) of afferent fibers. The basal synaptic response, measured in the absence of HFS, was not affected. The Schaffer collateral-CA1 synapse was not affected by AVP, even after LTP, while the Schaffer collateral-CA2 synapse was inhibited. Although investigated only recently, this CA2 hippocampal area appears to have a distinctive circuitry and a peculiar role in controlling episodic memory. Accordingly, AVP action on LTP-increased synaptic responses in this limbic structure may contribute to the role of this neuropeptide in controlling memory and social behavior.

Published
2012

16. Early hippocampal synaptic plasticity and episodic like-memory deficits in a transgenic mouse model of Alzheimer disease - involvment of corticosterone

Author

Ana Rita Salgueiro Peirera, Hélène Marie, Fabien Lanté, Magda Chafai, Ingrid Bethus, and Elisabeth F. Raymond

Subjects
Genetically modified mouse, biology, business.industry, Clinical Neurology, Hippocampus, Long-term potentiation, medicine.disease, Cellular and Molecular Neuroscience, chemistry.chemical_compound, chemistry, Corticosterone, Episodic-like memory, Poster Presentation, Amyloid precursor protein, biology.protein, Medicine, Neurology (clinical), Alzheimer's disease, business, Long-term depression, Molecular Biology, Neuroscience
Abstract

Background The etiology of Alzheimer’s disease (AD) is unclear and no cure is yet available. The function of the hippocampus, a key structure responsible for memory encoding and consolidation, is affected early in AD leading to progressive irreversible memory loss. There is strong evidence that AD onset is, at least partly, due to accumulation within the hippocampus of peptides processed from the amyloid precursor protein APP, such as amyloid-beta (A?). Also, several studies demonstrated an abnormal elevation in the main stress hormone, cortisol (CORT in mice), in the initial phase of AD in patients and in mouse models. Here, we investigated if early co-accumulation of CORT and APP-derived peptides could be a main trigger driving the onset of memory deficits in AD.

Published
2013

Catalog

Books, media, physical & digital resources
See catalog results