July 07, 1990 - July 07, 2023

  • Date:14SundayOctober 2018

    Serotonin and Autism Therapeutics: Insights from Human Mutations and Mouse Models

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    Gerhard M.J. Schmidt Lecture Hall
    Dr. Randy Blakely
    Director, Florida Atlantic University New Brain Institute, Florida
    Department of Neurobiology
    DetailsShow full text description of Host: Prof. Menahem Segal Menahem.segal@weizmann.ac.il tel: ...»
    Host: Prof. Menahem Segal Menahem.segal@weizmann.ac.il tel: 2553
    For assistance with accessibility issues, please contact naomi.moses@weizmann.ac.il
    AbstractShow full text abstract about Signs of serotonergic dysfunction appeared more than 50 year...»
    Signs of serotonergic dysfunction appeared more than 50 years ago with findings of hyperserotonemia in a subset of subjects with ASD, work replicated in multiple studies across the years, and accompanied by supportive data in human and animal studies. Owing to the early elaboration of serotonergic neurons in the mammalian CNS, and genetic evidence for male-specific linkage to ASD overlying the SERT gene locus, we screened multiplex ASD families for evidence of penetrant coding variants in the serotonin transporter, SERT, reporting these in 2005 and evidence that the most common of these, SERT Ala56, demonstrates alterations in the three core domains of the disorder when introduced into the mouse genome, in 2012. More recently, we have identified signaling pathways that lead to aberrant hyperactivity of SERT Ala56 in vitro and in vivo, leading to a novel therapeutic approach, involving manipulation of p38 MAPK. The talk will review the history of the work and next steps in understanding the serotonergic contribution to ASD features arising from other mutations and environmental perturbations.