PROJECT: JTC2015: RESPOND

Role of serotonin in the pathogenesis of neurodevelopmental disorders

Abstract

RESPOND responds to the increasing burden on patients and societies imposed by neurodevelopmental disorders such as attention-deficit hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and schizophrenia. The neurotransmitter serotonin has been implicated in the pathogenesis of these diseases and is a known regulator of neurodevelopment. However, the relevance of serotonin for the pathogenesis of these diseases and the involved mechanisms remain to be clarified. RESPOND will analyze neurodevelopmental processes and disease-related behavior in three novel rat strains with targeted genetic alterations in two major components of the serotonin system, TPH2, the serotonin-synthesizing enzyme, and SERT, the serotonin reuptake transporter. Rats offer more suitable behavioral assays for the research on ADHD, ASD, and schizophrenia than mice and are therefore the preferred animal model. In parallel pluripotent stem cells will be isolated from patients with these diseases and from the rats with dysregulated central serotonin system and used to assess alterations in differentiation and in-vitro as well as in-vivo development. The five partners from Germany, Poland, France, and The Netherlands will join their highly complementary expertise in RESPOND to provide a comprehensive description of serotonin?s role in neurodevelopmental disorders and eventually establish novel animal and cellular models for the development of therapies for ADHD, ASD, and schizophrenia.

Keywords

Gene targeting in the brain, Stem cells and neural differentiation/cell therapy, Molecular modelling techniques, Imaging techniques, Pharmacology, Behavioural methodologies, (epi)genetic approaches, "omics" approaches, Clinical trial, omics approaches, Stem cells and neural differentiation/cell therapy, serotonin, Neurodevelopmental visual disorders, Sox2, COUP-TF1, gene regulatory networks, cell reprogramming, Restless legs Syndrome, RLS, Meis1, Striatum

Call topic

Neurodevelopmental Disorders

Proposed runtime

2016 - 2018

Project team

Michael Bader (Coordinator)
Germany (BMBF)
Klaus Lesch
Germany (BMBF)
Piotr Popik
Poland (NCBR)
Patricia Gaspar
France (ANR)