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

该建议旨在评估硒（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，氧化应激和炎症是连接饮食、外周组织和大脑发育的关键过程。将给怀孕和哺乳期的雌性大鼠及其后代提供两种硒含量不同的等热量饮食，直至成年。硒在支持大脑和行为发育方面的作用也将在铅（Pb）存在的情况下进行评估，铅是一种环境压力源，能够影响认知发展，这是一些欧洲国家关注的问题。该项目分为5个工作包，旨在剖析不同饮食对行为发育、认知功能、海马体突触可塑性以及周围和中枢炎症的影响。体外和体外方法，转录组学，蛋白质组学，代谢组学/脂质组学，不同靶器官氧化应激和炎症途径的测量。不同年龄的两性后代将被分开考虑，以强调神经发育的性别差异。从正在进行的欧盟人类出生队列中获得的观察结果将加强实验研究，该队列测量了儿童接触铅，微量营养素，生活方式与认知，语言和运动发育评估的关系。

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.