Sex-dependent influence of prenatal lipid levels on brain development

拟议研究计划的主要目标是调查产前血脂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，人们对脂类激活的信号通路的特征产生了极大的兴趣。大脑的健康发展有赖于前列腺素E2(PGE2)等脂质的供应。这种主要的脂质分子自然存在于大脑中，对调节大脑早期发育及其正常功能所需的必要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，从而导致各种大脑缺陷。*产前大脑发育经历不断的变化，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。这项研究计划将提供证据，证明怀孕期间这些脂分子的异常水平会影响必要发育基因的表达、神经细胞的组织、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建议的那样，研究PGE2水平的变化扰乱发育中的大脑的分子机制将是理解它们如何促进大脑病理的关键。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。这对于评估为什么一些神经发育障碍在男性中的患病率更高是有价值的。最后，我们的研究可能会提高人们对环境风险因素的认识，这些因素可能会影响怀孕期间的血脂水平。

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.**