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 disorders in the affected offspring. Related to this, an important goal of our work is to explore the impact of MIA effects across the lifespan. In this context, we recently reported the effects of poly (I:C)-induced MIA at gestational day (GD)15, immediately prior to birth, at GD21 and again at post-natal day (PD)21, providing a systematic assessment of plasma IL-6, body temperature and weight alterations in pregnant rats following poly (I:C) exposure and preliminary evidence for gross morphological changes and microglial neuropathology in both male and female offspring at GD21 and PD21. Here, we sought to complement and extend these data by characterising in more detail the meso-scale impact of gestational poly (I:C) exposure at GD15 on the neuroanatomy of the juvenile (PD21) rat brain using high-resolution, ex vivo anatomical magnetic resonance imaging (MRI) in combination with atlas-based segmentation. Our preliminary data suggest subtle neuroanatomical effects of gestational poly (I:C) exposure (n=10) relative to saline controls (n=10) at this time-point. Specifically, we report here preliminary evidence for a significant increase in the relative volume of the diagonal domain in poly (I:C) offspring (p<0.01; q<0.1), particularly in female offspring. This occurred in the absence of any microstructural alterations as detectable using diffusion tensor imaging (DTI). Longitudinal in vivo studies, informed by the effect sizes from this dataset are now required to establish both the functional relevance and cellular mechanisms of the apparent DD volume increase.