Selenium in early life to enhance neurodevelopment in unfavourable settings
The project aimed at evaluating the specific role of selenium (Se) in relation to other nutrients and trace elements in favoring brain and behavioral plasticity. The central hypothesis tested is the role of oxidative stress and inflammation as key processes connecting diet, peripheral tissues and brain development. In our experimental models, pregnant and lactating female rats and their offspring till adulthood were fed with isocaloric diets differing in Se content. The role of Se in supporting brain and behavior development was assessed both per se and in the presence of lead (Pb), an environmental stressor able to affect cognitive development that is a concern in some European countries.
The project consisted of 5 work packages aimed at dissecting the effects of the different diets on behavioral 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, namely brain, liver and adipose tissues. The offspring of the two sexes at different ages were separately considered to assess sex-differences in neurodevelopment. The experimental studies were reinforced by the observations obtained from an ongoing EU human birth cohort (the Polish Mother and Child Cohort) where exposure to Pb, micronutrients, lifestyle have been measured in children in association with assessment of cognitive, language and motor development.
Both experimental studies and human cohort observations indicate a detrimental effect of suboptimal Se intake on behavioural development and the adverse influence of early exposure to Pb in the absence of optimal Se intake. Our results also underline the effects of dietary Se on neuroinflammation and neuroplasticity.
Altogether, the results of the project point to the importance of nutritional education in pregnancy to promote brain and behavior development; these results could have an impact on the consumption habits, to ameliorate health of populations suffering from partial selenium deficiency and exposed to chemical stressors, in particular during pregnancy and in childhood.
|Parner Organization||Partner Country|
|University of Montpellier - ENSCM||France|
|University of Wuerzburg||Germany|
|Università degli Studi di Milano||Italy|
|Nofer Institute of Occupational Medicine||Poland|
|University of East Anglia||United Kingdom|
- Experimental in vivo studies indicate that SubOptimal Se intake, from preconception through juvenile stage, causes behavioral changes in neonatal and juvenile rats. At tissue level, SubOptimal Se intake causes an altered pattern of inflammatory gene expression in brain, with long-term consequences especially in the Cortex; a decrease in the expression of the most relevant subunits of glutamatergic receptors; a decrease of liver enzymatic antioxidant system; an extensive deregulation of gene expression in adipose tissue.
- Experimental in vivo studies indicate that Optimal Se intake counteracts the effect of developmental exposure to low doses of lead. At neuronal level, Se neutralizes the effects lead on the organisation of glutamatergic system in dependence of the dose and sex, resulting protective in males at optimal dose.
- In vitro analyses confirm that microglia, the major immune population within the brain, are significantly affected by SubOptimal Se intake and their abnormalities are responsible for the altered neuroinflammatory levels.
- Human studies in the Polish Mother and Child cohort confirm the experimental model findings as for the detrimental effects of Se deficiency on behavioural development and the adverse influence of early exposure to Pb in the absence of optimal Se intake.