Sex-dependent influence of prenatal lipid levels on brain development

这项研究计划的主要目的是调查产前脂质水平在男性和女性大脑发育中的作用。由于越来越多的证据表明脂质在神经系统的功能中起着至关重要的作用，因此人们对表征它们激活的信号通路非常感兴趣。大脑的健康发育依赖于脂质的供应，如前列腺素E2（PGE2）。这种在大脑中天然存在的主要脂质分子在调节早期大脑发育及其正常功能所需的必需基因的表达方面非常重要。在怀孕期间，PGE2水平会受到各种环境因素的影响，如饮食，感染，空气污染物，药物如乙酰水杨酸或对乙酰氨基酚和化妆品中的化学物质，并导致各种大脑缺陷。 出生前的大脑发育经历着不断的变化，其正常功能在很大程度上取决于特定基因在任何特定时间的存在。这项研究计划将提供证据表明，怀孕期间这些脂质分子的异常水平可以影响重要发育基因的表达，神经元细胞的组织，大脑结构以及与称为Wnt的主要发育途径的相互作用。正如我们的研究计划所提出的，研究PGE 2水平变化扰乱大脑发育的分子机制对于了解它们如何导致大脑病理至关重要。这项研究还将进一步了解这些分子变化如何影响男性和女性的大脑。这将是有价值的评估为什么一些神经发育障碍的患病率是男性较高。最后，我们的研究可能会提高人们对怀孕期间可能影响血脂水平的环境风险因素的认识。

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.