Molecular and Environmental Influences on Autism Pathophysiology
University of California, Los Angeles
Basic & Clinical
Multiple studies have reported abnormal brain growth in people with autism, reflected by a larger head size early in development. This feature, called “macrocephaly” is determined in part by the number of times a cell divides as the brain matures. Using a cell culture technique, this study will examine genetic mutations of two genes associated with autism, PTEN and TSC on cell size and number. In addition to genetic influences, environmental factors could influence head size and cell division in the developing brain through production of reactive oxygen species (ROS). At low doses that are not toxic to neurons, these molecules have been known to produce changes in cell number. The current study will examine if ROS stimulates cell division through a similar pathway as PTEN and TSC mutations. The effects of prenatal exposure to low levels of ROS on cells with and without mutations of the PTEN gene will be assessed in parallel models to determine the interaction of the two on both brain size and cell number. What this means for people with autism: Both genetic susceptibility and environmental factors have been linked to the cause of autism. This research will help scientists understand the basic neurobiology behind enlarged head size in people with autism, as well as isolate a specific molecular mechanism where environmental influences can interact with genetic factors to produce macrocephaly.