Maternal immune activation in rodent models: A systematic review of neurodevelopmental changes in gene expression and epigenetic modulation in the offspring brain

Highlights

• Methodological heterogeneity contributes to differences in outcome measures.

• Gene ontologies map to pathways relevant to theorised disease aetiology.

• Epigenetic analyses are limited but suggest roles for these mechanisms in mIA-models.

• Directionality of changes demonstrate key functional pathways disturbed by mIA.

• We highlight the strength of mIA-models in preclinical research of NDD pathology.

Abstract

Maternal immune activation (mIA) during pregnancy is hypothesised to disrupt offspring neurodevelopment and predispose offspring to neurodevelopmental disorders such as schizophrenia. Rodent models of mIA have explored possible mechanisms underlying this paradigm and provide a vital tool for preclinical research. However, a comprehensive analysis of the molecular changes that occur in mIA-models is lacking, hindering identification of robust clinical targets. This systematic review assesses mIA-driven transcriptomic and epigenomic alterations in specific offspring brain regions. Across 118 studies, we focus on 88 candidate genes and show replicated changes in expression in critical functional areas, including elevated inflammatory markers, and reduced myelin and GABAergic signalling proteins. Further, disturbed epigenetic markers at nine of these genes support mIA-driven epigenetic modulation of transcription. Overall, our results demonstrate that current outcome measures have direct relevance for the hypothesised pathology of schizophrenia and emphasise the importance of mIA-models in contributing to the understanding of biological pathways impacted by mIA and the discovery of new drug targets.