Maternal immune activation and sex modulate hippocampal microglial properties in developing mice and result in behavioral changes in adult mice
Date
2024
Authors
Loewen, Sophia
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Maternal immune activation (MIA) is an inflammatory response during pregnancy that can result in an increased likelihood for the exposed offspring to develop neurodevelopmental disorders. MIA can be reliably induced in mouse models using polyinosinic:polycytidylic acid (poly I:C) at embryonic day 9.5, when microglia are colonizing the brain. Microglia, the resident immune cells of the brain, play critical roles during development though these roles vary throughout development, especially in the context of MIA. Furthermore, there is regional variability to microglia, including following MIA. We chose to focus on the polymorphic layer (PO) of the dentate gyrus and the cornu ammonis 1 (CA1) region (specifically the stratum radiatum (SR) and stratum lacunosum-moleculare (SLM)) of the ventral hippocampus as we know these regions are heavily involved in emotion and stress regulation—things that can be altered/involved in neurodevelopmental disorders. In these regions, we investigated microglial changes in density by staining against ionized calcium-binding adapter molecule 1 (Iba1; a typical microglial marker) and C-type lectin domain family 7 member A CLEC7a (pattern recognition receptor expressed on the surface of myeloid cells, including altered microglial states) in postnatal day 15 male and female mice. We show that CLEC7a-positive (+) cells have a tendency to increase in density in the CA1 SR region of the ventral hippocampus in MIA-exposed male P15 mice. We also highlight sex differences in development, namely that females have a lower density of Iba1+ cells compared to males at P15. We also show from our behavioral testing that females display slightly more anxiety-like behavior in adulthood. This work highlights the importance of continuing to investigate sex differences in microglia during development, both in the context of MIA and in health, as it may influence altered behavior in adulthood and may represent a window of potential therapeutic intervention.
Description
Keywords
Microglia, Development, Maternal immune activation, Mouse model