Maternal Immune Activation imprints translational dysregulation and differential MAP2 phosphorylation in descendant neural stem cells

ABSTRACT: To undertake a comprehensive examination of the molecular mechanisms governing the alterations induced by maternal immune activation (MIA) during gestation that impacts the subsequent neurodevelopment of progeny, we have devised an in vitro model based on neural stem cells (NSCs) sourced from fetuses carried by animals subjected to Poly I:C treatment. These neural progenitors demonstrate proliferative properties and can be effectively differentiated into both neurons and glial cells. Through transcriptomic, proteomic, and phosphoproteomic analyses conducted on these cellular models, in conjunction with counterparts from control treatments, discernible shifts in the expression levels of a specific subset of proteins implicated in neuronal function were elucidated. Noteworthy is the absence of congruence between these alterations and the transcriptomic findings, suggesting a potential dysregulation at the level of protein translation. Furthermore, a discernible discrepancy in the basal phosphorylation of proteins was observed between differentiated cells from both experimental groups, particularly within proteins associated with cytoskeletal architecture and synaptic functionality, notably those belonging to the MAP family. These observed alterations were found to correlate with changes in neuronal function, particularly with respect to synaptic plasticity and the establishment of neuronal synapses, thereby reaffirming previous assertions regarding the potential impact of MAP2 function modulation via its phosphorylation state on neuronal structure and function.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Stem Cell, Cell Culture, Early Embryonic Cell

DISEASE(S): Mixed Disorder As Reaction To Stress

SUBMITTER: Sandra M Martin-Guerrero  

LAB HEAD: Pedro R. Cutillas

PROVIDER: PXD056291 | Pride | 2025-02-16

REPOSITORIES: pride