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      Chronic sodium bromide relieves autistic-like deficits in the Oprm1 mouse model of autism and modulates the activity of serotonin and dopamine receptors in vitro

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          Abstract

          Chronic sodium bromide relieves autistic-like deficits in the Oprm1 mouse model of autism and modulates the activity of serotonin and dopamine receptors in vitro

          C. DERIEUX 1, S. ROUX 1, A. LEAUTE 1, T. PLOUVIER 2, J.A.J. BECKER 1, J. LE MERRER 1

          1 Déficits de Récompense, GPCRs et Sociabilité, Physiologie de la Reproduction et des Comportements, INRA UMR0085, CNRS UMR7247, Université de Tours, Inserm ; 37380 Nouzilly, France

          2 Térali Innov, 37230 Fondettes, France

          Corresponding author : cecile.derieux@inra.fr

          Autism spectrum disorders (ASD) are complex neurodevelopmental diseases whose diagnosis lies on the detection of impaired social skills together with restricted and repetitive behavior and interests (DSM-5). Although the etiology of ASD remains mostly unknown, impaired excitation/inhibition ratio appears as a common mechanistic feature. Bromide ion is known to reduce hyperexcitability, possibly by competing with chloride ions at channels and transporters and may thus have therapeutic potential in ASD.

          Aims : We evaluated the therapeutic potential of bromide ion in the Oprm1 -/- mouse model of ASD and the molecular mechanisms involved in bromide treatment, notably effects on GPCRs.

          Methods : In vivo, we first assessed the effect of chronically administered sodium bromide on autistic-like behavioral deficits and performed RT-qPCR on brain structures known to be involved in ASD. In vitro, we evaluated the impact of bromide ion on G-protein mediated signaling of serotonin and dopamine receptors.

          Results : In vivo, sodium bromide (30 to 500 mg/Kg) dose-dependently improved social interaction and preference, reduced stereotypies and decreased anxiety. Bromide also impacts the expression of genes coding for some GPCRs, chloride transporters and GABA A subunits. In vitro, bromide behaves as a positive allosteric modulator of 5-HT 6, 5-HT 7 and D1 receptors but not 5-HT 4 and D2 receptors.

          Conclusions : The beneficial effects of bromide administration in a genetic murine model of ASD and its impact on both gene expression and GPCR pharmacology predicts high translational potential in patients with autism, despite high heterogeneity in etiology and symptoms.

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          Author and article information

          Journal
          ScienceOpen Posters
          ScienceOpen
          1 July 2020
          Affiliations
          [1 ] INRAE
          [2 ] Universite de Strasbourg
          [3 ] Terali Innov
          Article
          10.14293/S2199-1006.1.SOR-.PP6VMC5.v1

          This work has been published open access under Creative Commons Attribution License CC BY 4.0 , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Conditions, terms of use and publishing policy can be found at www.scienceopen.com .

          The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

          Life sciences

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