Behavioural and developmental consequences of maternal immune activation in offspring

母体免疫激活对后代的行为和发育后果

• 批准号: 1791568
• 金额: --
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1791568
• 关键词: Behavioural; developmental; consequences; maternal; immune

One of the fundamental questions in basic disease research is how stressors experienced during critical periods influence the development of adult disease. In particular, stressors experienced during pregnancy have been shown to have effects on the propensity to develop cognitive disorders in offspring. But is this because of a change directly affecting brain development in utero or is it because mothers change their parental behaviour in response to stressors, or a combination? Further, what are the mechanisms underlying such effects? The placenta plays a critical role in maternal-fetal interactions and fetal adaptive responses in utero which may lead to a propensity to disease development later on in life. Prior work has indicated that placental development is affected by maternal stressors, but it remains unclear whether and how this may result in cognitive impairment in offspring. The proposed project seeks to answer these questions by applying a multidisciplinary approach to map functional changes along a developmental timeline that links placental morphological development to offspring traits, achieved by combining experimental studies in a rodent model system with evaluation of placental morphological development, together with parent-offspring behavioural interactions, cognitive and behavioural analyses. This will be combined with histological investigations and molecular array studies. This will also be complemented by a bioinformatics component to unravel the biological pathways and genetic networks of known candidates for placental function and associated behavioural impairments. The project therefore offers broad scientific training that will cover mammalian disease and behaviour research, histology, physiology, molecular biology, genetics and bioinformatics.

基础疾病研究中的一个基本问题是在关键时期经历的压力如何影响成人疾病的发展。特别是，怀孕期间经历的压力已被证明对后代发展认知障碍的倾向有影响。但是，这是因为一种直接影响子宫内大脑发育的变化，还是因为母亲为了应对压力而改变了父母的行为，或者两者兼而有之？此外，这种效应的机制是什么？胎盘在母体-胎儿相互作用和子宫内胎儿适应性反应中起着关键作用，这可能导致以后生活中疾病发展的倾向。先前的研究表明，胎盘发育受到母体压力的影响，但目前尚不清楚这是否以及如何导致后代的认知障碍。拟议的项目旨在回答这些问题，通过应用多学科的方法来映射功能变化沿着发展的时间轴，胎盘形态发育的后代性状，通过结合啮齿动物模型系统中的实验研究与胎盘形态发育的评价，以及亲子行为的相互作用，认知和行为分析。这将与组织学研究和分子阵列研究相结合。这也将由生物信息学组成部分来补充，以解开胎盘功能和相关行为障碍的已知候选人的生物途径和遗传网络。因此，该项目提供广泛的科学培训，涵盖哺乳动物疾病和行为研究、组织学、生理学、分子生物学、遗传学和生物信息学。