Chronic sodium bromide treatment relieves autistic-like behavioral deficits in three mouse models of autism
| Autor: | Cécile Derieux, Audrey Léauté, Agathe Brugoux, Déborah Jaccaz, Claire Terrier, Jean-Philippe Pin, Julie Kniazeff, Julie Le Merrer, Jerome A. J. Becker |
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| Přispěvatelé: | Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Unité Expérimentale de Physiologie Animale de l‘Orfrasiére (UE PAO), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Guerineau, Nathalie C. |
| Rok vydání: | 2021 |
| Předmět: |
Pharmacology
Bromides Mice Knockout Behavior Animal Autism Spectrum Disorder [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health Microfilament Proteins Nerve Tissue Proteins Receptors GABA-A Sodium Compounds Psychiatry and Mental health Disease Models Animal Fragile X Mental Retardation Protein Mice [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology Animals [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Autistic Disorder Social Behavior |
| Zdroj: | Neuropsychopharmacology Neuropsychopharmacology, 2022, 47 (9), pp.1680-1692. ⟨10.1038/s41386-022-01317-1⟩ |
| ISSN: | 1740-634X 0893-133X 0007-0920 |
| Popis: | International audience; Autism Spectrum Disorders (ASD) are neurodevelopmental disorders whose diagnosis relies on deficient social interaction and communication together with repetitive behavior. To date, no pharmacological treatment has been approved that ameliorates social behavior in patients with ASD. Based on the excitation/inhibition imbalance theory of autism, we hypothesized that bromide ions, long used as an antiepileptic medication, could relieve core symptoms of ASD. We evaluated the effects of chronic sodium bromide (NaBr) administration on autistic-like symptoms in three genetic mouse models of autism: Oprm1-/-, Fmr1-/- and Shank3Δex13-16-/- mice. We showed that chronic NaBr treatment relieved autistic-like behaviors in these three models. In Oprm1-/- mice, these beneficial effects were superior to those of chronic bumetanide administration. At transcriptional level, chronic NaBr in Oprm1 null mice was associated with increased expression of genes coding for chloride ions transporters, GABAA receptor subunits, oxytocin and mGlu4 receptor. Lastly, we uncovered synergistic alleviating effects of chronic NaBr and a positive allosteric modulator (PAM) of mGlu4 receptor on autistic-like behavior in Oprm1-/- mice. We evidenced in heterologous cells that bromide ions behave as PAMs of mGlu4, providing a molecular mechanism for such synergy. Our data reveal the therapeutic potential of bromide ions, alone or in combination with a PAM of mGlu4 receptor, for the treatment of ASDs. |
| Databáze: | OpenAIRE |
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