Prepubertal Stress Following Mild Maternal Immune System Activation Damages Prefrontal White MatterStructure and Related Molecules in Adult Mice Offspring

Abstract

Mild maternal immune activation (MIA) by inflammatory agents such as lipopolysaccharide (LPS) and prepubertal stress (PS) may individually and collectively affect the central nervous system (CNS) during adulthood. Here, we intend to assess the effects of mild MIA, alone or combined with PS, on prefrontal white matter structure and its related molecules in adult mice offspring. Pregnant mice received either a mild intraperitoneal (IP) dose of LPS (50 μg/kg) on gestational day 17 (GD17) or normal saline. Their pups were exposed to stress from postnatal days (PD) 30 to PD38 or no stress during prepubertal development. We randomly chose 56-day-old male offspring (n=2 offspring per mother) from each group and isolated their prefrontal areas according to relevant protocols. The tissue samples were prepared for structural, histological, and molecular examinations. According to the results, the LPS+stress group had evidence of increased damage in the white matter structures compared to the control, stress, and LPS groups (p<.05). The LPS+stress group also had significant downregulation of the genes involved in white matter formation (Sox10, Olig1, myelin regulatory factor (Aprato et al), and Wnt) compared to the control, stress, and LPS groups (p<.05).In conclusion, although each manipulation individually resulted in small changes in myelination, their combined effects were more pronounced. These changes were parallel to abnormal expression levels of the molecular factors that contribute to myelination.