Estrogens alleviate hyperactivity in zebrafish with autism gene

Research led by UCL, Yale and University of California, San Francisco has shown that the hormone estrogen alleviates the sleep disruption experienced by zebrafish genetically designed to help understand the biology of autism spectrum disorder (ASD). The scientists set out to investigate the function of genes linked to autism and seizures in humans by using zebrafish as a model system. They unexpectedly found that estrogens have a selective effect in calming hyperactive fish during the night which will help scientists to understand the brain pathways affected in ASD. The finding is also intriguing given ASD is four times more common in men than women. Co-corresponding author, Dr Jason Rihel, UCL Cell & Developmental Biology, said: "We're surprised to see that estrogens in particular have such a selective effect in correcting hyperactive behaviour in our ASD fish model, and we're investigating this further to understand the mechanisms of this response. We don't know if the hormone is targeting single or multiple pathways, as estrogen is involved in lots of processes, but we're keen to find out." The team discovered that a plant-derived estrogen, called biochanin A, and the human sex hormone, ?-estradiol, were most effective at selectively stopping night time hyperactivity without affecting the daytime activity of the fish. The FDA approved drug risperidone, which was the first approved to treat irritability and aggressive behaviour in ASD patients, stopped hyperactivity but made fish less active during the day, suggesting estrogens are better at selectively targeting pathways that are relevant to ASD.