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Topic

Maternal immune activation and sex modulate hippocampal microglial properties in developing mice and result in behavioral changes in adult mice

Division of Medical Sciences

Date & location

• Tuesday, March 4, 2025
• 1:00 P.M.
• Medical Sciences Building, Room 160

Examining Committee

Supervisory Committee

• Dr. Marie-Eve Tremblay, Division of Medical Sciences, University of Victoria (Supervisor)
• Dr. Hector Caruncho, Division of Medical Sciences, UVic (Member)
• Dr. Bob Chow, Department of Biology, UVic (Outside Member)

External Examiner

• Dr. Clare Beasley, Department of Psychiatry, University of British Columbia

Chair of Oral Examination

• Dr. Xiaodai Dong, Department of Electrical and Computer Engineering, UVic

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 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 learning, memory and emotion—all 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 the ventral hippocampus of postnatal day 15 male and female mice. We show that CLEC7a-positive (+) cells increase in density in the CA1 SR region of the ventral hippocampus in MIA-exposed male P15 mice, with females following a similar tendency. 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.