Redox signaling during neurodevelopment and sensitivity to oxidative stress

Project Summary:
Genetic susceptibilities and environmental insults together shape risk of developmental
disorders. Identifying convergent pathways among diverse risk factors is critical to developing
therapeutic targets. One such candidate pathway is oxidative stress. However, the role of
oxidation-reduction (redox) signaling in neurodevelopment is poorly understood. We will
address this gap by characterizing redox signaling during normal forebrain neurodevelopment in
mice and its response to environmental exposures. Using a genetically encoded redox sensitive
fluorescent biosensor, we will determine the redox state of developing neurons at critical
developmental timepoints. Embryos will then be exposed to the known oxidant herbicide
paraquat and acetaminophen to determine the sensitivity of neuron subclasses to oxidative
stress during different developmental stages. A commonly used antipyretic in pregnancy,
acetaminophen metabolites deplete cellular antioxidants, making cells more susceptible to
oxidative stress. The response of developing neurons to redox modifying compounds like
paraquat and acetaminophen are of substantial clinical and

Grant Number: 1R03ES036405-01A1
NIH Institute/Center: NIH
Principal Investigator: Melissa Campbell