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

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

Serotonin (5-HT), partially regulated by the 5-HT transporter (5-HTT), acts as both a neurotransmitter and a neurotrophic factor. In humans, the low-activity allelic variant of the 5-HTT-linked polymorphic region (5-HTTLPR s-allele) is associated with elevated 5-HT levels, which are linked to increased anxiety and heightened sensitivity to environmental stimuli. This allele is present in approximately 15% to 19% of the human population and is of particular interest due to its influence on stress reactivity and susceptibility to mental health conditions such as anxiety disorders and neurodevelopmental disorders (NDDs). Emerging evidence suggests that maternal 5-HT levels can affect offspring neurodevelopment not only through genetic inheritance but also through environmental pathways. These include prenatal exposure via the placenta and postnatal influences through maternal behavior. While genetic predispositions cannot be changed, maternal care is a modifiable factor. This makes it a promising target for early-life interventions aimed at improving developmental outcomes and reducing the risk of NDDs. This project aims to investigate whether environmental enrichment can improve maternal care and, in turn, promote better neurodevelopment in offspring, particularly in the context of altered serotonin levels. In this study, the well-established 5-HTT knockout (5-HTT−/−) rats are used to model humans with the HTTLPR s-allele. I examined how offspring were affected by maternal genotypes (5-HTT+/+ vs. 5-HTT-/-) and housing conditions (standard vs. enriched). Behavioral assessments, including ultrasonic vocalization (USV) analysis, are conducted from infancy through adulthood to capture developmental trajectories. Preliminary findings suggest that elevated 5-HT levels impair motor function in early life and contribute to increased anxiety and altered cognitive function in later developmental stages, such as young adulthood. Importantly, maternal care plays a key role in shaping these outcomes in a sex-dependent manner. Ongoing analyses seek to determine whether environmental enrichment can mitigate genotype-related deficits in maternal care and serve as a non-pharmacological intervention to support offspring development. This project highlights the importance of gene–environment interactions and modifiable early-life conditions in shaping lifelong mental health trajectories, and ultimately contributes to the growing emphasis on preventive and personalized interventions that support maternal and child well-being.

Data: CORDIS, © European Union