The Role of Lipid Mediator Prostaglandin E2 in Early Neuronal Development

Lipid mediator prostaglandin E2 (PGE2) plays a pivotal role in early development of the nervous system. Abnormal PGE2 signaling in neurodevelopment has also been implicated in autism. Increased levels of PGE2 have been attributed to maternal infection and the inflammatory response. My in vitro work shows that elevated levels of PGE2 cause an increase in cytosolic and growth cone calcium levels in differentiated neuroectodermal (NE-4C) cells and a dose- and time-dependent effect on neurite extension length. Furthermore, PGE2 induced subcellular localization of the EP4 receptor to the plasma membrane in NE-4C stem cells and growth cones of differentiated NE-4C cells. My in vivo work shows that prenatal exposure to PGE2 results in differential mRNA levels of two important developmental genes Wnt3a and Fosl1 in the mouse brain at various embryonic stages. This furthers our understanding of the functional implications of abnormal PGE2 signaling in the neurodevelopment of autism.