Prenatal administration of IL-1Ra attenuate the neurodevelopmental impacts following non-pathogenic inflammation during pregnancy

Abstract Prenatal inflammation negatively affects placental function, subsequently altering fetal development. Pathogen-associated molecular patterns (PAMPs) are used to mimics infections in preclinical models but rarely detected during pregnancy. Our group previously developed an animal model of pr...

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Autores principales:	Marie-Eve Brien, Katia Hughes, Sylvie Girard
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c59d3ebc6c394d4fa9917c64b25a4dc0
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spelling	oai:doaj.org-article:c59d3ebc6c394d4fa9917c64b25a4dc02021-12-05T12:12:07ZPrenatal administration of IL-1Ra attenuate the neurodevelopmental impacts following non-pathogenic inflammation during pregnancy10.1038/s41598-021-02927-32045-2322https://doaj.org/article/c59d3ebc6c394d4fa9917c64b25a4dc02021-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-02927-3https://doaj.org/toc/2045-2322Abstract Prenatal inflammation negatively affects placental function, subsequently altering fetal development. Pathogen-associated molecular patterns (PAMPs) are used to mimics infections in preclinical models but rarely detected during pregnancy. Our group previously developed an animal model of prenatal exposure to uric acid (endogenous mediator), leading to growth restriction alongside IL-1-driven placental inflammation (Brien et al. in J Immunol 198(1):443–451, 2017). Unlike PAMPs, the postnatal impact of prenatal non-pathogenic inflammation is still poorly understood. Therefore, we investigated the effects of prenatal uric acid exposure on postnatal neurodevelopment and the therapeutic potential of the IL-1 receptor antagonist; IL-1Ra. Uric acid induced growth restriction and placental inflammation, which IL-1Ra protected against. Postnatal evaluation of both structural and functional aspects of the brain revealed developmental changes. Both astrogliosis and microgliosis were observed in the hippocampus and white matter at postnatal day (PND)7 with IL-1Ra being protective. Decreased myelin density was observed at PND21, and reduced amount of neuronal precursor cells was observed in the Dentate Gyrus at PND35. Functionally, motor impairments were observed as evaluated with the increased time to fully turn upward (180 degrees) on the inclined plane and the pups were weaker on the grip strength test. Prenatal exposure to sterile inflammation, mimicking most clinical situation, induced growth restriction with negative impact on neurodevelopment. Targeted anti-inflammatory intervention prenatally could offer a strategy to protect brain development during pregnancy.Marie-Eve BrienKatia HughesSylvie GirardNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marie-Eve Brien Katia Hughes Sylvie Girard Prenatal administration of IL-1Ra attenuate the neurodevelopmental impacts following non-pathogenic inflammation during pregnancy
description	Abstract Prenatal inflammation negatively affects placental function, subsequently altering fetal development. Pathogen-associated molecular patterns (PAMPs) are used to mimics infections in preclinical models but rarely detected during pregnancy. Our group previously developed an animal model of prenatal exposure to uric acid (endogenous mediator), leading to growth restriction alongside IL-1-driven placental inflammation (Brien et al. in J Immunol 198(1):443–451, 2017). Unlike PAMPs, the postnatal impact of prenatal non-pathogenic inflammation is still poorly understood. Therefore, we investigated the effects of prenatal uric acid exposure on postnatal neurodevelopment and the therapeutic potential of the IL-1 receptor antagonist; IL-1Ra. Uric acid induced growth restriction and placental inflammation, which IL-1Ra protected against. Postnatal evaluation of both structural and functional aspects of the brain revealed developmental changes. Both astrogliosis and microgliosis were observed in the hippocampus and white matter at postnatal day (PND)7 with IL-1Ra being protective. Decreased myelin density was observed at PND21, and reduced amount of neuronal precursor cells was observed in the Dentate Gyrus at PND35. Functionally, motor impairments were observed as evaluated with the increased time to fully turn upward (180 degrees) on the inclined plane and the pups were weaker on the grip strength test. Prenatal exposure to sterile inflammation, mimicking most clinical situation, induced growth restriction with negative impact on neurodevelopment. Targeted anti-inflammatory intervention prenatally could offer a strategy to protect brain development during pregnancy.
format	article
author	Marie-Eve Brien Katia Hughes Sylvie Girard
author_facet	Marie-Eve Brien Katia Hughes Sylvie Girard
author_sort	Marie-Eve Brien
title	Prenatal administration of IL-1Ra attenuate the neurodevelopmental impacts following non-pathogenic inflammation during pregnancy
title_short	Prenatal administration of IL-1Ra attenuate the neurodevelopmental impacts following non-pathogenic inflammation during pregnancy
title_full	Prenatal administration of IL-1Ra attenuate the neurodevelopmental impacts following non-pathogenic inflammation during pregnancy
title_fullStr	Prenatal administration of IL-1Ra attenuate the neurodevelopmental impacts following non-pathogenic inflammation during pregnancy
title_full_unstemmed	Prenatal administration of IL-1Ra attenuate the neurodevelopmental impacts following non-pathogenic inflammation during pregnancy
title_sort	prenatal administration of il-1ra attenuate the neurodevelopmental impacts following non-pathogenic inflammation during pregnancy
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c59d3ebc6c394d4fa9917c64b25a4dc0
work_keys_str_mv	AT marieevebrien prenataladministrationofil1raattenuatetheneurodevelopmentalimpactsfollowingnonpathogenicinflammationduringpregnancy AT katiahughes prenataladministrationofil1raattenuatetheneurodevelopmentalimpactsfollowingnonpathogenicinflammationduringpregnancy AT sylviegirard prenataladministrationofil1raattenuatetheneurodevelopmentalimpactsfollowingnonpathogenicinflammationduringpregnancy
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Prenatal administration of IL-1Ra attenuate the neurodevelopmental impacts following non-pathogenic inflammation during pregnancy

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