Embryo-restricted responses to maternal IL-17A promote neurodevelopmental disorders in mouse offspring.

Autor: Andruszewski D; Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.; Research School of Translational Biomedicine (TransMed), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.; Focus Program Translational Neurosciences (FTN), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany., Uhlfelder DC; Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.; Research School of Translational Biomedicine (TransMed), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany., Desiato G; Institute of Neuroscience - National Research Council, Milan, Italy.; IRCCS Humanitas Research Hospital, via Manzoni 56, 20089 Rozzano, Milan, Italy., Regen T; Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany., Schelmbauer C; Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany., Blanfeld M; Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany., Scherer L; Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany., Radyushkin K; Focus Program Translational Neurosciences (FTN), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.; Translational Animal Research Center (TARC), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany., Pozzi D; IRCCS Humanitas Research Hospital, via Manzoni 56, 20089 Rozzano, Milan, Italy.; Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Milan, Italy., Waisman A; Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.; Research School of Translational Biomedicine (TransMed), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.; Focus Program Translational Neurosciences (FTN), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.; Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany., Mufazalov IA; Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany. ilgiz.mufazalov@uni-mainz.de.; Research School of Translational Biomedicine (TransMed), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany. ilgiz.mufazalov@uni-mainz.de.; Focus Program Translational Neurosciences (FTN), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany. ilgiz.mufazalov@uni-mainz.de.; Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany. ilgiz.mufazalov@uni-mainz.de.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2024 Oct 10. Date of Electronic Publication: 2024 Oct 10.
DOI: 10.1038/s41380-024-02772-6
Abstrakt: Prenatal imprinting to interleukin 17A (IL-17A) triggers behavioral disorders in offspring. However, reported models of maternal immune activation utilizing immunostimulants, lack specificity to elucidate the anatomical compartments of IL-17A's action and the distinct behavioral disturbances it causes. By combining transgenic IL-17A overexpression with maternal deficiency in its receptor, we established a novel model of prenatal imprinting to maternal IL-17A (acronym: PRIMA-17 model). This model allowed us to study prenatal imprinting established exclusively through embryo-restricted IL-17A responses. We demonstrated a transfer of transgenic IL-17A across the placental barrier, which triggered the development of selected behavioral deficits in mouse offspring. More specifically, embryonic responses to IL-17A resulted in communicative impairment in early-life measured by reduced numbers of nest retrieval calls. In adulthood, IL-17A-imprinted offspring displayed an increase in anxiety-like behavior. We advocate our PRIMA-17 model as a useful tool to study neurological deficits in mice.
(© 2024. The Author(s).)
Databáze: MEDLINE
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