The Effect of impaired Cyclooxygenase 2 activity on gene regulation in the developing mouse brain and the role of PGE2 in oxidative stress production in Differentiated Neuronal Cells

Prostaglandin E2 (PGE2) is a signaling molecule derived from the lipid membrane through the enzyme cyclooxygenase2 (COX-2). These studies aim to investigate how changes in COX-PGE2 signalling can influence mouse gene expression and alter oxidative stress in neuronal cells. In study 1 we use microarray analysis to identify differentially expressed genes among males and females at embryonic day 16 (E16) and 19 (E19). Bioinformatics software outlined genes involved in mitochondrial function, inflammatory responses, and synaptic plasticity. In study 2, differentiated Neuroectodermal (NE-4C) stem cells were treated with two concentrations of PGE2. Fluorescence microscopy with MitoSox Red was used to measure superoxide production. Both concentrations of PGE2 significantly increased superoxide production in a dose-dependent manner. In summary, these results indicated that altered levels of PGE2 can result in abnormal expression of important developmental genes involved in the mitochondrial function, as well as production of reactive oxygen species (ROS).