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Beitragstitel Involvement of the Wnt-Signaling in Methylphenidate (Ritalin) treatment of ADHD
Beitragscode P05
  1. Cristine Marie Yde Ohki Psychiatric University Hospital Zurich Vortragender
  2. Natalie Walter Univeristät Zürich
  3. Audrey Bender University of Zurich
  4. Michelle Rickli University of Zurich
  5. Leandra Keusch University of Zurich
  6. Negar Vahdani University of Zurich
  7. Jasmin Pfister University of Zurich
  8. Leoni Grossmann University of Zurich
  9. Kristin Koppelmaa University of Zurich
  10. Christian Döring University of Zurich
  11. Anna Maria Werling University of Zurich
  12. Susanne Walitza Psychiatrische Universitätsklinik Zürich
  13. Edna Grünblatt University of Zurich
Präsentationsform Poster
  • T06 - ADHD
Abstract Attention-deficit hyperactivity disorder (ADHD) is one of the most common psychiatric disorders in children and adolescents affecting over 5% of the population worldwide. Methylphenidate (MPH), the first-line treatment for this neurodevelopmental disorder, seems to ameliorate brain maturational delays in ADHD patients, who might present a lag of up to 4 years compared to controls. However, molecular mechanisms involved in this process remains elusive. Genetic studies including recent findings from our group indicate a possible involvement of the Wnt signaling-pathway, known to play a fundamental role in neurodevelopment, orchestrating important cellular processes, such as proliferation, differentiation and maturation. By using induced pluripotent stem cells (iPSCs)-derived neural progenitor cells (NPCs) and forebrain cortical neurons (FCNs), we will test functional alterations in the Wnt-signaling in ADHD and its possible association with affected neurodevelopment seen in patients. Concomitantly, the hypothesis that MPH activates this pathway, while alleviating maturational delays, will be tested. To do so, luciferase reporter assays will be performed in both groups to analyze Wnt activation following treatment, whereas growth rates of iPSCs and NPCs and neuronal synaptogenesis will be measured in xCELLigence/Wst-1 assays and immunocytochemistry, respectively. Following the same reasoning, transcriptomics and protein expression of Wnt-related genes and proteins will be assessed in these three developmental stages. ADHD and control groups will be compared before and after MPH treatment. The results will facilitate the understanding of the effects of MPH treatment in ADHD at the molecular level in neural cell models, providing a unique window of opportunity to develop strategies, preventive measures and possible new therapeutic targets.