Validation of a Valproic Acid Model of Autism Spectrum Disorder to Study Microglial Function
Andreas Krumbein, Allison Escandon, Judith Jacinto
Department of Biology
Faculty Supervisor: Nicholas Silva
Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental disorder that is characterized by behavioral changes. Genetic and pharmacological animal models in mice and zebrafish recapitulate aspects of the cellular and behavioral phenotypes associated with ASD. Zebrafish are genetically similar to humans and increasingly being used to study ASD. One pharmacological model validated in both mice and zebrafish to induce ASD-like phenotypes is valproic acid (VPA). To study neuroimmune interactions in the brain, we first validated the VPA model and characterized behavior using the DanioVision system. Zebrafish exposed to VPA showed decreased average velocity and distance moved, as well as altered habituation to light stimulus throughout development. In addition, immunohistochemistry was used to observe changes in the predominant immune cell of the brain, microglia. VPA treatment increased microglia number throughout the entire brain suggesting a potential clinical target. Our results validate the VPA model and establish a role for microglia to further investigate neuroimmune mechanisms associated with ASD.