Prostaglandin E2 and misoprostol induce neurite retraction in Neuro-2a cells

Prostaglandin E2 (PGE2) is a key lipid-derived compound which mediates important physiological functions in the nervous system via activation of four EP receptors (EP1–4). Recent studies have shown that altered PGE2 signalling due to abnormal lipid peroxidation and oxidative stress may underlie some pathologies of the nervous system. The prenatal exposure to the drug misoprostol, a prostaglandin type E analogue, has also been linked to a number of neurodevelopmental defects. In the present study, we use ratiometric calcium imaging with fura-2AM as a calcium indicator to determine the effects of PGE2 and misoprostol on calcium homeostasis in growth cones of mouse neuroblastoma (Neuro-2a) cells. Our results show that both drugs increase the amplitude of calcium transients in growth cones of Neuro-2a cells and induce neurite retraction. Moreover, quantitative real-time PCR also revealed that the mRNA expression level of the four EP receptors was significantly higher during the neurogenesis period in mouse indicating the importance of PGE2 signalling in the nervous system.

Research highlights
► PGE2 and misoprostol increase the amplitude of calcium fluctuations in growth cones of Neuro-2a cells.
► PGE2 and misoprostol significantly reduce the length and number of neuronal extensions.
► PGE2 receptors EP1, EP2, EP3α and EP3β may play a role during neurogenesis.
► EP3γ receptor is ubiquitously expressed across development.
► E4 receptor appears to be prevalent in organogenesis.