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Mom matters: Expound the influence of the interaction between maternal 5-HTT genotype and maternal care on offspring’s individual neurodevelopment

Project description

The impact of the maternal serotonin system on offspring’s neurodevelopment

Serotonin (5-HT) serves as both a neurotransmitter and a neurotrophic factor, contributing to offspring’s neurodevelopment prenatally and postnatally. The maternal serotonin transporter (5-HTT) genotype is a significant yet often overlooked source of 5-HT that influences offspring’s development through the placenta. Meanwhile, maternal care, which is influenced by the 5-HTT genotype, also affects the offspring. By improving maternal caregiving behaviour, an avenue for an early intervention facilitating children’s neurodevelopment emerges. The MSCA-funded PARENT project is embarking on a pioneering journey to investigate how the maternal 5-HTT genotype impacts maternal caregiving behaviour and subsequently shapes offspring development from an individual perspective. Overall, this project seeks to unravel the intricate links between maternal 5-HTT genotype, offspring development, and their interaction.

Objective

Serotonin plays a prominent role in a wide range of psychiatric disorders. Importantly, serotonin (5-HT) is not only a neurotransmitter but also a neurotrophic factor during brain development, contributing to neurodevelopmental disorders (NDDs). One largely neglected source of 5-HT affecting development is maternal serotonergic genotype, which can influence offspring through the placenta and by changing maternal care behaviour. As a pediatrician, I am interested in the latter, as it -unlike the biological route- can be modified, providing an opening for early intervention for children with NDDs. Here, I will delineate for the first time how maternal serotonin transporter (5-HTT) genotype affects maternal care behaviour and impacts offspring development from an individual perspective.
To understand the influence of maternal 5-HTT genotype on offsprings development related to sex and genotype, I will use the well-established 5-HTT knockout (5-HTT-/-) rat modeling 5-HTT gene variance in humans and affecting maternal care. First, I will examine maternal care behaviours in wild-type and 5-HTT-/- mothers, and the developmental trajectories of male and female offspring with varying 5-HTT genotypes by tests assessing social and emotional behaviour from infancy to adulthood. Included are highly sophisticated analyzes of ultrasonic vocalizations, which I am an expert in. Second, I will elucidate the offsprings brain-wide neuronal activity pattern using cutting-edge brain clearing and 3D lightsheet microscopy. To test causality and provide a lead for an early intervention, I will determine if enrichment ameliorates maternal care and improves offspring development. This project is expected to uncover how mother genotype influences offspring development in the context of behaviours relevant to NDDs and whether the developmental trajectory can be improved through a non-pharmacological intervention.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2022-PF-01

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Coordinator

STICHTING RADBOUD UNIVERSITAIR MEDISCH CENTRUM
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 203 464,32
Address
GEERT GROOTEPLEIN 10 ZUID
6525 GA NIJMEGEN
Netherlands

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Region
Oost-Nederland Gelderland Arnhem/Nijmegen
Activity type
Higher or Secondary Education Establishments
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Total cost

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