Early or Late Gestational Exposure to Maternal Immune Activation Alters Neurodevelopmental Trajectories in Mice: An Integrated Neuroimaging, Behavioral, and Transcriptional Study

AbstractBackground Exposure to maternal immune activation (MIA) in utero is a risk factor for neurodevelopmental disorders later life. The impact of the gestational timing MIA exposure on downstream development remains unclear. Methods We characterized trajectories mice exposed viral mimetic poly I:C (polyinosinic:polycytidylic acid) either day 9 (early) or 17 (late) using longitudinal structural magnetic resonance imaging from weaning adulthood. Using multivariate methods, we related neuroimaging and behavioral variables time greatest alteration (adolescence/early adulthood) identified regions further investigation RNA sequencing. Results Early was associated with accelerated brain volume increases adolescence/early adulthood that normalized striatum, hippocampus, cingulate cortex. Similarly, alterations anxiety-like, stereotypic, sensorimotor gating behaviors observed adolescence late gestation had less anatomical profiles. Multivariate maps social, deficits dorsal ventral hippocampus anterior cortex, among others. most transcriptional changes were genes enriched fibroblast growth regulation, autistic behaviors, inflammatory pathways, microRNA regulation. Conclusions Leveraging an integrated hypothesis- data-driven approach linking brain-behavior transcriptome, found differentially affects offspring development. leads subthreshold deficits, whereas early perturbs mechanisms implicated disorders.