Prenatal Environmental Stressors Impair Postnatal Microglia Function and Adult Behavior in Males

Block, C. L.; Eroglu, O.; Mague, S. D.; Sriworarat, C.; Blount, C.; Malacon, K. E.; Beben, K. A.; Ndubuizu, N.; Talbot, A.; Gallagher, N.; Jo, Y. C.; Nyangacha, T.; Carlson, D.; Dzirasa, K.; Eroglu, C.; Bilbo, S. D.

doi:10.1101/2020.10.15.336669

bioRxiv · 10.1101/2020.10.15.336669

Prenatal Environmental Stressors Impair Postnatal Microglia Function and Adult Behavior in Males

Block, C. L.·Eroglu, O.·Mague, S. D.·Sriworarat, C.·Blount, C.·Malacon, K. E.·Beben, K. A.·Ndubuizu, N.·Talbot, A.·Gallagher, N.·Jo, Y. C.·Nyangacha, T.·Carlson, D.·Dzirasa, K.·Eroglu, C.·Bilbo, S. D.

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Abstract

Gestational exposure to environmental toxins and socioeconomic stressors are epidemiologically linked to neurodevelopmental disorders with strong male-bias, such as autism. We modeled these prenatal risk factors in mice, by co-exposing pregnant dams to an environmental pollutant and limited-resource stress, which robustly activated the maternal immune system. Only male offspring displayed long-lasting behavioral abnormalities and alterations in the activity of brain networks encoding social interactions. Cellularly, prenatal stressors diminished microglial function within the anterior cingulate cortex, a central node of the social coding network, in males during early postnatal development. Genetic ablation of microglia during the same critical period mimicked the impact of prenatal stressors on a male-specific behavior, indicating that environmental stressors alter neural circuit formation in males via impairing microglia function during development.

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Block, C. L., Eroglu, O., Mague, S. D., Sriworarat, C., Blount, C., Malacon, K. E., Beben, K. A., Ndubuizu, N., Talbot, A., Gallagher, N., Jo, Y. C., Nyangacha, T., Carlson, D., Dzirasa, K., Eroglu, C., Bilbo, S. D.. 2020-10-19. Prenatal Environmental Stressors Impair Postnatal Microglia Function and Adult Behavior in Males. https://doi.org/10.1101/2020.10.15.336669

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