Metabolomic Analysis of Neural Precursor Cells Derived from Autism iPSCs and Their Response to Environmental Stressors decooShort Title
Autism is a complex neurodevelopmental disorder consisting of abnormal social interactions and repetitive and restricted movements and behaviors. The causes of autism lay with interactions of genetic changes with environmental factors. Further, the large variability in the types and degrees of autism symptoms suggests there are many â€œautismsâ€ that are due to individual differences that manifest themselves as fewer more common phenotypes. Thus studying specific individuals with autism may be key to knowing how to help them, so called personalized medicine. Significantly, the study of genetic and environmental factors in autism have necessarily focused on human tissues that are quite distant from the primary locus of disease, the developing human brain. Genetic studies have used peripheral blood cells or postmortem brain tissue, whereas environmental factors are discovered by epidemiological observations, associating toxins with disease prevalence in the population. Subsequently, causative factors have been studied in cell or rodent models to define mechanisms and possible therapies. This study also tests directly on human neurons and precursors the effects of possible environmental stressors that may be associated with autism. This will reveal whether some individuals are genetically susceptible to neurotoxins, a question impossible to address in rodent models. More generally, with this information, we may better describe the multifaceted changes that occur across the range of genetic and epigenetic to metabolic states that produce the autism related phenotypes we are currently defining in iPSCs and neurons. In turn, therapeutic interventions using available drugs can be developed to ameliorate abnormal neuronal development in autism at multiple levels of entry.