Teratogen induced ASD and brainstem development
National Institute for Medical Research
While the etiology of autism and ASD is unknown, prenatal exposure to chemical teratogens including the antiseizure medications thalidomide and valproate are associated with increased incidences of ASD. Exposure to these agents is known to produce brainstem abnormalities which are reflected in individuals with autism. While the mechanism by which these defects are caused by these chemicals is being explored, the findings do raise the possibility that they may be similar to that which contributes to autism neuropathology. This project proposes to initiate a detailed analysis of the effect of thalidomide and valproate on different species of animals, including the rat, mouse, chick and zebrafish. The investigators will examine a panel of molecular markers – genes which will identify specific structures in the developing brainstem. The identification of chemical induced brain defects in these organisms will offer the opportunity for many follow up studies to determine the exact nature of the flaws and how they cause the symptoms of ASD. Significance: Because exposure to thalidomide and valproate has been associated with symptoms of autism spectrum disorder, an understanding of the specific biochemical and molecular effects of these teratogens during early brainstem development will help better identify disease mechanism. This information is likely to have far-reaching implications for understanding and diagnosing ASD and may aid the development of therapeutic interventions to treat or ameliorate ASD symptoms.