Fetal neuroinflammation and prenatal stress (PS) may contribute to lifelong
neurological disabilities. Astrocytes and microglia play a pivotal role, but
the mechanisms are poorly understood. Here, we test the hypothesis that via
gene-environment interactions, fetal neuroinflammation and PS may reprogram
glial immunometabolic phenotypes which impact neurodevelopment and
neurobehavior. This glial-neuronal interplay increases the risk for clinical
manifestation of autism spectrum disorder (ASD) in at-risk children. Drawing on
genomic data from the recently published series of ovine and rodent glial
transcriptome analyses with fetuses exposed to neuroinflammation or PS, we
conducted a secondary analysis against the Simons Foundation Autism Research
Initiative (SFARI) Gene database. We confirmed 21 gene hits. Using unsupervised
statistical network analysis, we then identified six clusters of probable
protein-protein interactions mapping onto the immunometabolic and stress
response networks and epigenetic memory. These findings support our hypothesis.
We discuss the implications for ASD etiology, early detection, and novel
therapeutic approaches.Comment: Supplemental Table and Data:
https://github.com/martinfrasch/ASD_origins_hypothesis. arXiv admin note:
text overlap with arXiv:1812.06617 | This is a different study with related
research context (relevance to ASD