Tau Hypophosphorylation at Ser416 as the Early Molecular Imprint of Maternal Immune Activation: Insights from Female Mice Offspring.

Maternal immune activation (MIA) is a recognized environmental risk factor for altered brain development, yet its early molecular consequences remain unclear. In this study, we examined total Tau, site-specific Tau phosphorylation, and selected synaptic proteins in one-month-old female mouse offspring exposed prenatally to MIA evoked by poly(I:C), a synthetic mimetic of viral dsRNA. Our analyses revealed a consistent reduction in Tau phosphorylation at Ser416 across multiple brain regions, including the cortex, hippocampus, and cerebellum, without changes in total Tau levels or other phosphorylation sites. Among synaptic markers, only Shank3 levels were decreased, and this effect was confined to the cerebellum. No additional robust alterations were detected at this stage of development. These findings suggest that Tau hypophosphorylation at Ser416 may represent an early and widespread molecular footprint of MIA, whereas cerebellar Shank3 downregulation points to a region-specific vulnerability of synaptic pathways. While the study is limited to female offspring and a single postnatal time point, the data provide new insights into subtle molecular signatures that could precede or accompany later functional outcomes. Our results highlight Tau phosphorylation and Shank3 expression as potential molecular markers of prenatal immune stress, warranting further longitudinal and sex-comparative studies to clarify their relevance for neurodevelopmental trajectories.