Differential effects of early or late exposure to prenatal maternal immune activation on mouse embryonic neurodevelopment

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dc.contributor.authorGuma, Elisa
dc.contributor.authorBordeleau, Maude
dc.contributor.authorGonzález Ibáñez, Fernando
dc.contributor.authorPicard, Katherine
dc.contributor.authorSnook, Emily
dc.contributor.authorDesrosiers-Grégoire, Gabriel
dc.contributor.authorSpring, Shoshana
dc.contributor.authorLerch, Jason P.
dc.contributor.authorNieman, Brian J.
dc.contributor.authorDevenyi, Gabriel A.
dc.contributor.authorTremblay, Marie-Ève
dc.contributor.authorChakravarty, M. Mallar
dc.date.accessioned2024-02-09T16:03:26Z
dc.date.available2024-02-09T16:03:26Z
dc.date.copyright2022en_US
dc.date.issued2022
dc.descriptionWe 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.en_US
dc.description.abstractExposure 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.en_US
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipFinally, we acknowledge our funding bodies, including the Canadian Institute of Health Research and Healthy Brains for Healthy Lives, for providing support for this research. Additionally, we thank the Fonds de Recherche du Québec en Santé for providing salary support for E.G., K.P., and M.M.C., as well as the Kappa Gamma Foundation of Canada for supporting the salary of E.G. M.-E.T. is a Tier 2 Canada Research Chair in Neurobiology of Aging and Cognition.en_US
dc.identifier.citationGuma, 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.2114545119en_US
dc.identifier.urihttps://doi.org/10.1073/pnas.2114545119
dc.identifier.urihttp://hdl.handle.net/1828/15976
dc.language.isoenen_US
dc.publisherPNASen_US
dc.subjectmaternal immune activation
dc.subjectembryo brain development
dc.subjectstructural MRI
dc.subjectelectron microscopy
dc.subjectbrain development
dc.subject.departmentDivision of Medical Sciences
dc.subject.departmentSchool of Medical Sciences
dc.titleDifferential effects of early or late exposure to prenatal maternal immune activation on mouse embryonic neurodevelopmenten_US
dc.typeArticleen_US

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