Selenium in early life to enhance neurodevelopment in unfavourable settings (SELENIUS)

该提案旨在评估硒（Se）与其他营养素和微量元素在促进大脑和行为可塑性方面的具体作用。我们将测试的中心假设是氧化应激和炎症作为连接饮食，外周组织和大脑发育的关键过程的作用。将两种含硒量不同的等热量饲料给予妊娠和哺乳期雌性大鼠及其后代直至成年。硒在支持大脑和行为发育中的作用也将在铅（Pb）的存在下进行评估，铅是一种能够影响认知发育的环境应激源，这在一些欧洲国家是一个值得关注的问题。该项目分为5个工作包，旨在解剖不同饮食对行为发育，认知功能，海马突触可塑性以及外周和中枢炎症的影响。离体和体外方法以及转录组学、蛋白质组学、代谢组学/脂质组学、不同靶器官中氧化应激和炎症途径的测量。不同年龄的两种性别的后代将被单独考虑，以强调神经发育的性别差异。实验研究将通过从正在进行的欧盟人类出生队列中获得的观察结果得到加强，在该队列中，已经测量了儿童的铅暴露、微量营养素和生活方式，并评估了认知、语言和运动发育。

The proposal aims at evaluating the specific role of selenium (Se) in relation to other nutrients and trace elements in favouring brain and behavioural plasticity. The central hypothesis we will test is the role of oxidative stress and inflammation as key processes connecting diet, peripheral tissues and brain development. Two isocaloric diets differing in Se content will be given to pregnant and lactating female rats and to their offspring till adulthood. The role of Se in supporting brain and behaviour development will be also assessed in presence of lead (Pb) an environmental stressor able to affect cognitive development that is a concern in some European countries. The project has been organized in 5 work packages aimed at dissecting the effects of the different diets on behavioural development, cognitive functions, hippocampal synaptic plasticity and peripheral and central inflammation, using. ex vivo and in vitro approaches and transcriptomic, proteomic, metabolomics/lipidomic, measurement of oxidative stress and inflammatory pathways in different target organs. The offspring of the two sexes at different ages will be separately considered to emphasize sex-differences in neurodevelopment. The experimental studies will be reinforced by the observation obtained from an ongoing EU human birth cohort where exposure to Pb, micronutrients, lifestyle have been measured in children in association with assessment of cognitive, language and motor development.