Influence of Oxidative Stress on Transcription and Alternative Splicing of Methionine Synthase in Autism
Many cases of autism are thought to develop due to environmental exposures acting on genetically vulnerable individuals. Potential environmental exposures encompass all non-genetic factors that might contribute to autism, including pesticides, manufacturing chemicals, heavy metals, and so on. These toxins are thought to impair biochemical or metabolic processes which are critical for normal development and normal cognitive function. Most of these toxins are thought to cause oxidative stress and inflammation, and studies of autistic children have shown evidence of these processes in their blood and brains. In this study, the predoctoral fellow will investigate the link between oxidative stress and metabolism in a system related to neuronal function. The vitamin B12-dependent enzyme methionine synthase is a metabolic protein that is extremely sensitive to environmental toxins, and levels of this enzyme have been found to be reduced in postmortem autistic brains. To determine whether the changes observed in brain samples can be detected non-invasively in patients, blood samples from autistic and control subjects will be analyzed for methionine synthase levels. This could prove to be a valuable blood test in the diagnosis of autism. As well, biochemical and cellular experiments will be conducted to investigate the mechanisms by which oxidative stress affects the level and functional properties of methionine synthase. This research may lead to a better understanding of the underlying mechanisms of environmental triggers in autism, as well as to a potential new tool for the diagnosis of autism.