Differential effects of early or late exposure to prenatal maternal immune activation on mouse embryonic neurodevelopment
Date
2022
Authors
Guma, Elisa
Bordeleau, Maude
González Ibáñez, Fernando
Picard, Katherine
Snook, Emily
Desrosiers-Grégoire, Gabriel
Spring, Shoshana
Lerch, Jason P.
Nieman, Brian J.
Devenyi, Gabriel A.
Journal Title
Journal ISSN
Volume Title
Publisher
PNAS
Abstract
Exposure to maternal immune activation (MIA) in utero is a risk factor for neurodevelopmental and psychiatric disorders. MIA-induced deficits in adolescent and adult offspring have been well characterized; however, less is known about the effects of MIA exposure on embryo development. To address this gap, we performed high-resolution ex vivo MRI to investigate the effects of early (gestational day [GD]9) and late (GD17) MIA exposure on embryo (GD18) brain structure. We identify striking neuroanatomical changes in the embryo brain, particularly in the late-exposed offspring. We further examined the putative neuroanatomical underpinnings of MIA timing in the hippocampus using electron microscopy and identified differential effects due to MIA timing. An increase in apoptotic cell density was observed in the GD9-exposed offspring, while an increase in the density of neurons and glia with ultrastructural features reflective of increased neuroinflammation and oxidative stress was observed in GD17-exposed offspring, particularly in females. Overall, our findings integrate imaging techniques across different scales to identify differential impact of MIA timing on the earliest stages of neurodevelopment.
Description
We are grateful to Roulin Gao for providing training in how to harvest embryos. We thank Drs. Bruno Giros and Salah El Mestikawy for lending us their centrifuge. A preprint of this work is available on BioRxiv (https://doi.org/10.1101/2021.07.14.452084), and all the data (preprocessed embryo brain MRIs and EM data from the dorsal hippocampus) have been made publicly available on the Zenodo platform (https://zenodo.org/record/5164621), as has the code used to perform statistical analyses.
Keywords
maternal immune activation, embryo brain development, structural MRI, electron microscopy, brain development
Citation
Guma, E., Bordeleau, M., González Ibáñez, F., Picard, K., Snook, E., Desrosiers-Grégoire, G., ... Chakravarty, M. M. (2022). Differential effects of early or late exposure to prenatal maternal immune activation on mouse embryonic neurodevelopment. PNAS, 119(12), e2114545119. https://doi.org/10.1073/pnas.2114545119