Sex-dependent influence of prenatal lipid levels on brain development

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The main objective of the proposed research program is to investigate the role of prenatal lipid levels in the male and female brain development. Because of the growing evidence about the vital role of lipids in the function of the nervous system there is a great interest in characterizing the signaling pathways that they activate. Healthy development of the brain relies on the supply of lipids such as prostaglandin E2 (PGE2). This major lipid molecule naturally found in the brain is important in regulating the expression of essential genes required for early brain development and its proper function. During pregnancy the PGE2 level can be influenced by various environmental factors such as diet, infections, air pollutants, drugs such as acetylsalicylic acid or acetaminophen and chemicals in cosmetics and result in various brain defects. ******Prenatal brain development undergoes constant changes and its normal functioning depends greatly on the presence of specific genes at any given time. This research program will provide evidence that abnormal levels of these lipid molecules during pregnancy can influence expression of essential developmental genes, organization of neuronal cells, brain architecture and interaction with the major developmental pathways called Wnt. As proposed in our research program, investigation into molecular mechanisms by which changes in PGE2 levels disrupt the growing brain will be crucial to understand how they may contribute to brain pathologies. This research will also add further knowledge into how these molecular changes impact the male and female brains. This will be valuable for evaluating why the prevalence of some neurodevelopmental disorders is higher in males. Lastly, our research might increase awareness of environmental risk factors that can influence the lipid levels during pregnancy.**