Sex-dependent influence of prenatal lipid levels on brain development

提出的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功能中的重要作用，人们对它们激活的信号通路的特征产生了极大的兴趣。大脑的健康发育依赖于像前列腺素E2 （PGE2）这样的脂质供应。这种天然存在于大脑中的主要脂质分子对调节早期大脑发育及其正常功能所需的基本基因的表达非常重要。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，并导致各种脑缺陷。产前大脑发育经历了不断的变化，其正常功能在很大程度上取决于特定基因在任何给定时间的存在。该研究项目将提供证据，证明孕期这些脂质分子的异常水平会影响重要发育基因的表达、神经元细胞的组织、大脑结构以及与主要发育途径Wnt的相互作用。正如我们在研究项目中提出的那样，研究PGE2水平的变化破坏大脑生长的分子机制对于理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。这对于评估为什么某些神经发育障碍的患病率在男性中较高是有价值的。最后，我们的研究可能会提高人们对怀孕期间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.