Developing Zebrafish Models to Study the Relationship Between the Gut Microbiome and Autism Susceptibility

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Senior Projects Spring 2015

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Caffrey, Elisa Benedetti
Bard Digital Commons
Autism; Zebrafish; Behavioral Testing; Microbiome; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Medical Education; Medical Immunology; Medical Microbiology; Medical Neurobiology; Neurology; Psychiatric and Mental Health
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Autism Spectrum Disorder (ASD) describes a range of neurodevelopmental disorders affecting 1 in 68 children in the United States (CDC 2014). ASD patients typically exhibit plasma hyperserotonemia and brain hyposerotonemia, indicating the serotonergic system plays a role in the autism phenotype. Serotonin is highly regulated by the gut microbiome and there is a specific signature in organism abundance in the gut microbiome of ASD patients. Zebrafish are an inexpensive vertebrate model system that develop rapidly and have a well-studied gut microbiome. To study the relationship between the gut microbiome and autism susceptibility, I derived germ-free (GF) zebrafish and created an autism-like zebrafish model using valproic acid (VPA), a common pharmaceutical used to induce autism in other model organisms. GF zebrafish displayed behavior consistent with a decrease in anxiety and a dysregulation in serotonin levels. VPA exposed zebrafish larvae displayed behavior consistent with an increase in anxiety, along with a dysregulation of serotonin levels. This study supports zebrafish as a model for ASD susceptibility, and allows for the creation of a gnotobiotic model to study the effects of species-specific abundance on the ASD phenotype and the impact of the gut microbiome on the serotonergic system, with implications for potential ASD treatment.