Preliminary evidence that maternal immune activation specifically increases diagonal domain volume in the rat brain during early postnatal development

Abstract

Maternal immune activation (MIA) is consistently associated with elevated risk for multiple psychiatric and neurological disorders in the affected offspring. Converging lines of evidence from humans and animal models suggest a link between MIA and early entry into an atypical neurodevelopmental trajectory characterised by time- and sex-dependent abnormalities in brain structure and function. However to date, no such studies have investigated the brain-wide impact of MIA in the early post-weaning period, a critical and dynamic window of brain development. To address this, we acquired high-resolution ex vivo structural and diffusion tensor imaging (DTI) images from Wistar rat brains on postnatal day (PD) 21 following exposure to the viral mimetic poly (I:C) or sterile saline on gestational day (GD) 15 using a recently validated protocol. Using a combination of atlas-based segmentation and tensor based morphometry analysis we observed that MIA resulted in a significant increase in the relative volume of the diagonal domain (FDR q<0.1). Additional trend-level volume increases (p<0.05 uncorrected) were also found for the olfactory structures and preoptic area. Although not significant after FDR correction, we found trend-level evidence (p<0.05 uncorrected) for MIA x sex interactions in the volume of the diagonal domain, nucleus accumbens, pineal gland and anterior commissure. In contrast to volume, we found no evidence for microstructural alterations in our DTI dataset at PD21. These data provide new insights into the specific effects of MIA early in development, highlighting in particular, the diagonal domain as a target for future studies.