The Negative Influence Of High-glucose Ambience On Neurogenesis In Developing Quail Embryos

Purpose: Gestational diabetes is defined as glucose intolerance during pregnancy and itis presented as high blood glucose levels during the onset pregnancy. This condition hasan adverse impact on fetal development but the mechanism involved is still not fullyunderstood. In this study, we investigated the effects of high glucose on the developingquail embryo, especially its impact on the development of the nervous system.Materials and results: We established that high glucose altered the central nervoussystem mophologically, such that neural tube defects (NTDs) developed. In addition, wefound that high glucose impaired nerve differentiation at dorsal root ganglia and in thedeveloping limb buds, as revealed by neurofilament (NF) immunofluorescent staining.The dorsal root ganglia are normally derived from neural crest cells (NCCs), so weexamine the delimination of NCCs from dorsal side of the neural tube. We establishedthat high glucose was detrimental to the NCCs, in vivo and in vitro. High glucose alsonegatively affected neural differentiation by reduced the number and length of neuritesemanating from neurons in culture. We established that high glucose exposure caused anincrease in reactive oxidative species (ROS) generation by primary cultured neurons. Wehypothesized that excess ROS was the factor responsible for impairing neurondevelopment and differentiation. We provided evidence for our hypothesis by showingthat the addition of vitamin C (a powerful antioxidant) could rescue the damaging effectsof high glucose on cultured neurons.Conclusions: Our study suggests that the malformations which developed in the neuraltube, dorsal root ganglia and nerves in the limb buds were the results of impaired NCCsdevelopment caused by excess ROS in presence of high glucose. It has been reported thatvitamin C supplements added to the diet of pregnant diabetic rats could reduced the rateof embryo malformations and fetal resorption. In another word, vitamin C could act as anantioxidant to neutralize excess ROS produced in embryonic tissues. Our study supportsthis idea because we demonstrated that adding vitamin C to our cultured neurons couldinhibit the damaging effects of high glucose on the neurons. Moreover, since we showedthat vitamin C decreases ROS generation, it implies that vitamin C exerted its effect by inhibiting ROS rather than directly protecting the cells.