Obiettivo Prenatal stress (PS) is more detrimental to males than to females. Evidence is accumulating that PS may play an important etiological role in the incidence of neurodevelopmental disorders, which often show a male bias in incidence. The mechanisms underlying the sex-specific effects of PS are still unknown, but recent evidence implicates a crucial role for microglia, the resident immune cells of the central nervous system. Although in the adult brain microglia are activated only after infection or injury, in the developing neonate microglia show a structurally activated pattern, especially in males, which coincides with the critical period for hormonal action that cause sexual differentiation of the brain. Very recently the immune system, with a central role for microglia cells, was found to play a pivotal role in the masculinizing pathway. I hypothesize that the sex-specific behavioral vulnerability to PS is caused by sex-specific activation of neonatal microglia, leading to deficits in synaptic pruning, through epigenetic alterations in microglia, most notable in the COX2 promoter. COX2 is pivotal in the feed-forward mechanism of microglia activation and implicated in neurodevelopmental disorders. I will induce or block neonatal microglia activation to study whether PGE2 is both necessary and sufficient to induce the sex-specific vulnerability to PS and its mechanisms. These experiments may give important novel insights into the sex-specific sensitivity to the prenatal environment, and help understand the male predominance in many neurodevelopmental disorders. Coming from a world-leading lab with the main focus on sex differences in the brain I will bring important new knowledge and techniques to the host institute, while I will be thoroughly trained in state-of-the-art techniques at the interface of neuroscience and immunology at the country’s best research university, creating a novel niche in the field and preparing me for a professorship position in the EU. Campo scientifico natural sciencesbiological sciencesneurobiologymedical and health sciencesbasic medicineimmunologysocial scienceseconomics and businesseconomicsproduction economicsproductivitynatural sciencesbiological scienceszoologymammalogymedical and health sciencesbasic medicineneurology Programma(i) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Argomento(i) MSCA-IF-2014-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Invito a presentare proposte H2020-MSCA-IF-2014 Vedi altri progetti per questo bando Meccanismo di finanziamento MSCA-IF-EF-RI - RI – Reintegration panel Coordinatore UNIVERSITAIR MEDISCH CENTRUM UTRECHT Contribution nette de l'UE € 177 598,80 Indirizzo HEIDELBERGLAAN 100 3584 CX Utrecht Paesi Bassi Mostra sulla mappa Regione West-Nederland Utrecht Utrecht Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 177 598,80