Periodic Reporting for period 1 - FOODFORLIFE (Life-long cross-generational priming of the hypothalamus for obesity)
Okres sprawozdawczy: 2022-01-01 do 2023-06-30
This project puts forward the hypothesis that maternal nutrient supply and hormonal influences could effectively "program" foetal organ development. We posit that the hypothalamus, which acts as the neuroendocrine interface linking the brain and periphery, could particularly be affected. Maternal obesity could evoke permanent molecular changes in hypothalamic neurons and glia of the offspring to compromise their plasticity and adaptive repertoire.This notion is on the backdrop of our recent success in defining, by singe-cell RNA-seq and brain-wide imaging, the developmental trajectory of neurons that build the mammalian hypothalamus, and in discovering the function of novel neuronal subtypes. Using our preliminary data, we will build a comprehensive atlas of hypothalamic cell types that undergo prenatal "programming" when mothers are exposed, in preclinical models, to specific nutrients to find "access points" to intervene with impaired brain development. Moreover, we will mechanistically interrogate the developmental trajectories, functional competences, and neurodevelopmental vulnerabilities of specific neurocircuits, and if their malformation (and/or malfunction) is causal to metabolic diseases in affected offspring.
2) We have discovered novel astrocyte-neutron signaling systems, their sensitivity to maternal nutrient availability, and effects on synapse maturation,
3) We have described novel associations of hormones/neuropeptides and fast neurotransmitters with a view on brain-wide input/output connectivity and functional coupling.