Selenium in early life to enhance neurodevelopment in unfavourable settings
|Partner 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|
1. Overall project description
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.
-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.
4.1 List of publications
|Authors||Title||Year, Issue, PP||Partners Number||Doi|
|Calamandrei G, Ricceri L, Tartaglione AM, Polańska K, Chiarotti F.||Pregnancy exposome and child psychomotor development in three European birth cohorts.||2020 Feb;181:108856.||10.1016/j.envres.2019.108856.||Download|
|Calamandrei G, Polańska K.||Sociodemographic, Lifestyle, Environmental and Pregnancy-Related Determinants of Dietary Patterns during Pregnancy.||2019 Mar 2;16(5):754.||10.3390/ijerph16050754.||Download|
|Tartaglione AM, Minghetti L, Ricceri L, Cubadda F, Calamandrei G, Viviani B.||Sex-Dependent Effects of Developmental Lead Exposure in Wistar Rats: Evidence from Behavioral and Molecular Correlates.||2020 Apr 11;21(8):2664.||10.3390/ijms21082664||Download|
|K. Polanska, F. Chiarotti, G. Calamandrei.||Sex-Dependent Impact of Low-Level Lead Exposure during Prenatal Period on Child Psychomotor Functions.||2018;15(10):2263.||10.3390/ijerph15102263||Download|
|Polanska K, Chiarotti F, Calamandrei G.||Micronutrients during pregnancy and child psychomotor development: Opposite effects of Zinc and Selenium.||2017;158:583-589.||10.1016/j.envres.2017.06.037||Download|
|Kinga Polanska, Gemma Calamandrei, Flavia Chiarotti||Selenium status during pregnancy and child psychomotor development—Polish Mother and Child Cohort study||2016, 79(6); 863-869||10.1038/pr.2016.32||Download|
4.2 Presentation of the project
|Target group||Authors||Means of communication||Hyperlink|
|scientist||Tartaglione AM, Attorri L, Ricceri L, Cubadda F, Raggi A, Di Biase A, D'Archivio M, Serafini M, Locatelli N, Viviani B, Ajmone-Cat MA, De Simone R, Minghetti L , Polanska K and Calamandrei G The critical role of selenium in brain development: protection from low-dose lead toxicity and sex-dependent effects on behavior, neuroplasticity and inflammatory markers in a rat model . International Neurotoxicology Association Meeting, Dusseldorf (Germany) September 28-October 1st 2019||Poster|
|scientists||Polańska K, Calamandrei G, The critical role of selenium in brain development: protection from low-dose lead toxicity and sex-dependent effects on behavior, neuroplasticity and inflammatory markers in a rat model INCHES Meeting, to be held in Amsterdam on April 22-26 2020, postponed to December 2020||Poster|
|scientists, policy makers||Ajmone-Cat MA, De Simone R, D'Archivio M, Varì R, Di Biase A, Attorri L, Calamandrei G, Tartaglione AM, Cubadda F, Raggi A, Ricceri L, Viviani B, Polanska K, Fairweather S, Durand T, Sauer S, Sunaga-Franze D, Kliem M, and Minghetti L. “A multidisciplinary approach to study the critical role of Selenium in brain development and functioning in unfavourable setting (SELENIUS): effects of early life diet on inflammation and oxidative stress”. 5th Conference “A HEALTHY DIET FOR A HEALTHY LIFE” and “Agenda of the JPI HDHL FINAL SYMPOSIA”, 20-21 feb 2019, Bruxelles||Poster|
|scientists, policy makers||Calamandrei G, Tartaglione AM, Scalfari A, Attorri L Ricceri L. Cubadda F, Raggi A, Di Biase A, D'Archivio M, Marchetti N, Gerosa L, Viviani B. Ajmone-Cat MA, De Simone R, Polanska K, and Minghetti L. “A multidisciplinary approach to study the critical role of early life nutrition in brain development: from birth cohorts to animal studies and backwards in the SELENIUS project”. 5th Conference “A HEALTHY DIET FOR A HEALTHY LIFE” and “Agenda of the JPI HDHL FINAL SYMPOSIA”, 20-21 feb 2019, Bruxelles||Poster|
|Scientists||Ajmone-Cat MA, De Simone R, Tartaglione AM, Calamandrei G, Ricceri L, Attorri L, Cubadda F, Raggi A, Di Biase A, D'Archivio M, Viviani B, and Minghetti L. “Selenium intake in early life affects neurodevelopment and the neuroinflammatory response”. “XIV European Meeting on glial cells in health and disease” Oporto, Portugal, July 10-13th 2019||Poster|
|Scientists||Ajmone-Cat M.A. “Selenium intake in early life affects neurodevelopment and the neuroinflammatory response” Neuroscienze Romane Seminar Series, University of Rome “La Sapienza”, Italy 2019||Oral presentation|
|scientist, policy makers||Ajmone-Cat MA, De Simone R, T and Minghetti L. Open day on Alzheimer: “ISS e malattia di Alzheimer: prevenzione oltre la diagnosi” June 4th 2019, ISS, Rome, Italy.||Poster and discussion|
|scientists||Calamandrei G, Cubadda F, Di Biase A, D'Archivio M, Viviani B. Ajmone-Cat MA, De Simone R, Polanska K, and Minghetti L. Final meeting of the project “Selenium In Early Life To Enhance Neurodevelopment In Unfavourable Settings (SELENIUS), 31st of May 2019, Istituto Superiore di Sanità, Rome, Italy||oral presentation|
|D'Archivio M, Franze D. and Minghetti L. Evaluating the impact of Se deficiency in early life on adipose tissue signature and molecular networks identifying correlations with brain and cognitive dysfunctions. 3rd Food Bioactives and Health Congress - to be held in Parma on June 16-19 2020, postponed to December 2020||poster|
|medical doctors||B. Viviani Neurodevelopment and environmental contaminants: the state of the art. Milanopsichiatria, Milan 2019||Oral presentation|
|Young scientists||Melania Maria Serafini, Annamaria Tartaglione, Silvia Tangianu, Gaia Sara Silvia Serra, Francesco Cubadda, Gemma Calamandrei, Luisa Minghetti, Barbara Viviani. Selenium in early life as a strategy to promote neurodevelopment after lead exposure. Brayn, Milan 2019.||Poster|
|Young scientists||Silvia Tangianu, Gaia Sara Silvia Serra, Annamaria Tartaglione, Melania Maria Serafini, Francesco Cubadda, Gemma Calamandrei, Luisa Minghetti, Barbara Viviani. The role of selenium intake in brain development: focus on the glutamatergic system. Brayn, Milan 2019||Poster|
|Scientists||Melania Maria Serafini, Annamaria Tartaglione, Silvia Tangianu, Gaia Sara Silvia Serra, Irene Cattaneo, Iman Khattat, Francesco Cubadda, Gemma Calamandrei, Luisa Minghetti, Barbara Viviani. Selenium intake and brain health: focus on the glutamatergic system and the Selenium transport machinery in the hippocampus. FENS Forum 2020, Virtual||Poster|
|scientists||Melania Maria Serafini, Anna Maria Tartaglione, Silvia Tangianu, Gaia Sara Silvia Serra, Irene Cattaneo, Iman Khattat, Francesco Cubadda, Luisa Minghetti, Gemma Calamandrei, Barbara Viviani. Dimorfismo sessuale nella neurotossicità indotta da esposizione perinatale al Piombo e nell’effetto protettivo esercitato da una dieta addizionata di Selenio. Congresso Nazionale della Società Italiana di Tossicologia (SITOX), Bologna, 2020||Oral communication|
|Scientists and policy makers||Calamandrei G, Tartaglione AM, Scalfari A, Attorri L, Ricceri L, Cubadda F, Raggi A, Di Biase A, D'Archivio M, Marchetti N, Gerosa L, Viviani B, Ajimone-Cat MA, De Simone R, Polanska K and Minghetti L A multidisciplinary approach to study the critical role of early life nutrition in brain development: from birth cohorts to animal studies and backwards in the SELENIUS project . Prenatal Programming and Toxicity (PPTOX) 2018 meeting., Faroe Islands (DK), May 26-30 2018||Oral and poster presentation|
|Scientists and policy makers||Polanska K, Hanke W, Kałużny P, Trafalska E. G. Calamandrei. Correlates of maternal diet during pregnancy. K. Polanska, A. Krol, D. Merecz-Kot, D. Ligocka, K. Mikolajewska, F. Mirabella, F. Chiarotti, G. Calamandrei, W. Hanke. Impact of micronutrients during pregnancy on children’s health and neurodevelopment The 9th International Conference on Children's Health and the Environment: Saving the Children at Risk, Shaping the Future Sustainability - South Korea (Seul) 06.2018)||Poster|
|Scientists and Students||Calamandrei G Tartaglione AM, Scalfari A, Attorri L, Ricceri L, Cubadda F, Aureli F, Di Biase A, D'Archivio M, Marchetti N, Gerosa L, Viviani B, Ajmone-Cat MA, De Simone R, Minghetti L. The critical role of essential micronutrients in brain and behaviour development: evidence from in vivo studies on dietary selenium deficiency. 16th Meeting of Italian Society for Neurosciences, Ischia (Napoli) October 1-4 2017||Poster|
|Scientists and students||Gerosa L., Marchetti N., Catelli V., Locatelli N., Galli C. L., Marinovich M., Viviani B. Impatto dell’esposizione a basse dosi di piombo sulla maturazione del sistema glutammatergico in neuroni primari di ippocampo. National congress of the Italian Society of Toxicology (SITOX), Bologna, April 10-13 2018||Poster|
|Scientists and students||L. Gerosa, Anna Maria Tartaglione, S. Mancino, N. Marchetti, Alessandro Scalfari, Laura Ricceri, N. Locatelli, V. Catelli, Francesco Cubadda, Andrea Raggi, Luisa Minghetti, Gemma Calamandrei, B. Viviani. Valutazione dell’impatto del sesso sulla neurotossicità indotta dall’esposizione perinatale a piombo. National congress of the Italian Society of Toxicology (SITOX), Bologna, 10-13 aprile 2018.||Poster|
|Scientists||Polanska K, Hanke W, Krol A, Gromadzinska J, Kuras K, Janasik B, Wasowicz, Mirabella F, Chiarotti F, Calamandrei G. Micronutrients during pregnancy and child psychomotor development: opposite effects of Zinc and Selenium. The 10th anniversary World Congress” Developmental Origins of Health and Diseases (DOHaD) Rotterdam, The Netherlands. 15-18.10.2017||Poster|
|Young scientists||Ewelina Wesołowska. Micronutrients during pregnancy and their impact on child neurodevelopment. JPI HDHL conference. Belgium, Brussels 01.12.2017.||Oral presentation|
|Young scientists||Anna Maria Tartaglione. The critical role of micronutrients in neurodevelopment: short- and long-term behavioral outcome in a Selenium-deficient rat model. JPI HDHL conference. Belgium, Brussels 01.12.2017.||Oral presentation|
|Scientists||Polanska K, Krol A, Gromadzinska J, Brodzka R, Calamandrei G, Chiarotti F, Merecz-Kot D, Makowiec-Dabrowska T, Ligocka D, Wasowicz W, Hanke W. Maternal lifestyle during pregnancy and child neurodevelopment. 8th International Conference on Children's Health and the Environment 14th – 16th September 2016, Barcelona (Spain)||Oral presentation|
|Scientists||Polanska K, Krol A, Ligocka D Merecz-Kot D, Jurewicz J, Makowiec-Dabrowska T, Chiarotti Calamandrei G, Hanke W. Selenium status during pregnancy and child neurodevelopment. 28th Annual Conference International Society for Environmental Epidemiology. 1-4 September 2016. Rome (Italy)||Poster|
4.3 List of submitted patents and other outputs
|Patent licence||Partners involved||Year||International eu or national patent||Comment|