CD200-CD200R imbalance correlates with microglia and pro-inflammatory activation in rat spinal cords exposed to amniotic fluid in retinoic acid-induced spina bifida

Abstract Spina bifida aperta is a congenital malformation characterized by the failure of neural tube closure resulting in an unprotected fetal spinal cord. The spinal cord then undergoes progressive damage, likely due to chemical and mechanical factors related to exposure to the intrauterine enviro...

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Autores principales:	Marc Oria, Rebeca L. Figueira, Federico Scorletti, Lourenco Sbragia, Kathryn Owens, Zhen Li, Bedika Pathak, Maria U. Corona, Mario Marotta, Jose L. Encinas, Jose L. Peiro
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d27350b9eb1f42c3bb062607cab6445c
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spelling	oai:doaj.org-article:d27350b9eb1f42c3bb062607cab6445c2021-12-02T15:07:58ZCD200-CD200R imbalance correlates with microglia and pro-inflammatory activation in rat spinal cords exposed to amniotic fluid in retinoic acid-induced spina bifida10.1038/s41598-018-28829-52045-2322https://doaj.org/article/d27350b9eb1f42c3bb062607cab6445c2018-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-28829-5https://doaj.org/toc/2045-2322Abstract Spina bifida aperta is a congenital malformation characterized by the failure of neural tube closure resulting in an unprotected fetal spinal cord. The spinal cord then undergoes progressive damage, likely due to chemical and mechanical factors related to exposure to the intrauterine environment. Astrogliosis in exposed spinal cords has been described in animal models of spina bifida during embryonic life but its relationship with neuroinflammatory processes are completely unknown. Using a retinoic acid-induced rat model of spina bifida we demonstrated that, when exposed to amniotic fluid, fetal spinal cords showed progressive astrogliosis with neuronal loss at mid-gestation (E15) compared to unexposed spinal cords. The number of microglial cells with a reactive phenotype and activation marker expression increased during gestation and exhibited progressive disruption in the inhibitory immune ligand-receptor system. Specifically we demonstrate down-regulation of CD200 expression and up-regulation of CD200R. Exposed spinal cords demonstrated neuroinflammation with increased tissue water content and cytokine production by the end of gestation (E20), which correlated with active Caspase3 expression in the exposed layers. Our findings provide new evidence that microglia activation, including the disruption of the endogenous inhibitory system (CD200-CD200R), may participate in the pathogenesis of spina bifida through late gestation.Marc OriaRebeca L. FigueiraFederico ScorlettiLourenco SbragiaKathryn OwensZhen LiBedika PathakMaria U. CoronaMario MarottaJose L. EncinasJose L. PeiroNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marc Oria Rebeca L. Figueira Federico Scorletti Lourenco Sbragia Kathryn Owens Zhen Li Bedika Pathak Maria U. Corona Mario Marotta Jose L. Encinas Jose L. Peiro CD200-CD200R imbalance correlates with microglia and pro-inflammatory activation in rat spinal cords exposed to amniotic fluid in retinoic acid-induced spina bifida
description	Abstract Spina bifida aperta is a congenital malformation characterized by the failure of neural tube closure resulting in an unprotected fetal spinal cord. The spinal cord then undergoes progressive damage, likely due to chemical and mechanical factors related to exposure to the intrauterine environment. Astrogliosis in exposed spinal cords has been described in animal models of spina bifida during embryonic life but its relationship with neuroinflammatory processes are completely unknown. Using a retinoic acid-induced rat model of spina bifida we demonstrated that, when exposed to amniotic fluid, fetal spinal cords showed progressive astrogliosis with neuronal loss at mid-gestation (E15) compared to unexposed spinal cords. The number of microglial cells with a reactive phenotype and activation marker expression increased during gestation and exhibited progressive disruption in the inhibitory immune ligand-receptor system. Specifically we demonstrate down-regulation of CD200 expression and up-regulation of CD200R. Exposed spinal cords demonstrated neuroinflammation with increased tissue water content and cytokine production by the end of gestation (E20), which correlated with active Caspase3 expression in the exposed layers. Our findings provide new evidence that microglia activation, including the disruption of the endogenous inhibitory system (CD200-CD200R), may participate in the pathogenesis of spina bifida through late gestation.
format	article
author	Marc Oria Rebeca L. Figueira Federico Scorletti Lourenco Sbragia Kathryn Owens Zhen Li Bedika Pathak Maria U. Corona Mario Marotta Jose L. Encinas Jose L. Peiro
author_facet	Marc Oria Rebeca L. Figueira Federico Scorletti Lourenco Sbragia Kathryn Owens Zhen Li Bedika Pathak Maria U. Corona Mario Marotta Jose L. Encinas Jose L. Peiro
author_sort	Marc Oria
title	CD200-CD200R imbalance correlates with microglia and pro-inflammatory activation in rat spinal cords exposed to amniotic fluid in retinoic acid-induced spina bifida
title_short	CD200-CD200R imbalance correlates with microglia and pro-inflammatory activation in rat spinal cords exposed to amniotic fluid in retinoic acid-induced spina bifida
title_full	CD200-CD200R imbalance correlates with microglia and pro-inflammatory activation in rat spinal cords exposed to amniotic fluid in retinoic acid-induced spina bifida
title_fullStr	CD200-CD200R imbalance correlates with microglia and pro-inflammatory activation in rat spinal cords exposed to amniotic fluid in retinoic acid-induced spina bifida
title_full_unstemmed	CD200-CD200R imbalance correlates with microglia and pro-inflammatory activation in rat spinal cords exposed to amniotic fluid in retinoic acid-induced spina bifida
title_sort	cd200-cd200r imbalance correlates with microglia and pro-inflammatory activation in rat spinal cords exposed to amniotic fluid in retinoic acid-induced spina bifida
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/d27350b9eb1f42c3bb062607cab6445c
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CD200-CD200R imbalance correlates with microglia and pro-inflammatory activation in rat spinal cords exposed to amniotic fluid in retinoic acid-induced spina bifida

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