Aberrant astrocyte protein secretion contributes to altered neuronal development in diverse disorders

Astrocytes negatively impact neuronal development in a range of neurodevelopmental disorders (NDs), however how they do this, and if mechanisms are shared across multiple disorders, is not known. We developed an in vitro system to ask how astrocyte protein secretion and gene expression change in 3 genetic NDs (Fragile X syndrome (FXS), Rett's syndrome (RTT), Down's syndrome (DS)). This identified disorder specific changes, as well as core proteins that are increased in release in all 3 NDs. We provide a resource of astrocyte secreted proteins and gene expression in health and NDs, as well as novel targets for intervention in diverse NDs. Astrocytes isolated from the P7 mouse cortex of WT, FXS, RTT, DS mice using immunopanning. Maintained in vitro in defined serum free media for 12 days before RNA collection. Biological replicates for NDs: WT=6, FXS=6, RTT=6, DS=4. For comparing gene expression in WT astrocytes treated with BMP6, WT astrocytes were treated for the last 5 days of the culture period with BMP6 or left untreated (Alone condition). Biological replicates for BMP6: Alone=6, BMP6=6.