Prenatal activation of microglia induces delayed impairment of glutamatergic synaptic function.

<h4>Background</h4>Epidemiological studies have linked maternal infection during pregnancy to later development of neuropsychiatric disorders in the offspring. In mice, experimental inflammation during embryonic development impairs behavioral and cognitive performances in adulthood. Syna...

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Autores principales:	Anne Roumier, Olivier Pascual, Catherine Béchade, Shirley Wakselman, Jean-Christophe Poncer, Eleonore Réal, Antoine Triller, Alain Bessis
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/94994fbe8816427c814024dac0fcffad
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spelling	oai:doaj.org-article:94994fbe8816427c814024dac0fcffad2021-11-25T06:11:43ZPrenatal activation of microglia induces delayed impairment of glutamatergic synaptic function.1932-620310.1371/journal.pone.0002595https://doaj.org/article/94994fbe8816427c814024dac0fcffad2008-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18612411/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Epidemiological studies have linked maternal infection during pregnancy to later development of neuropsychiatric disorders in the offspring. In mice, experimental inflammation during embryonic development impairs behavioral and cognitive performances in adulthood. Synaptic dysfunctions may be at the origin of cognitive impairments, however the link between prenatal inflammation and synaptic defects remains to be established.<h4>Methodology/principal findings</h4>In this study, we show that prenatal alteration of microglial function, including inflammation, induces delayed synaptic dysfunction in the adult. DAP12 is a microglial signaling protein expressed around birth, mutations of which in the human induces the Nasu-Hakola disease, characterized by early dementia. We presently report that synaptic excitatory currents in mice bearing a loss-of-function mutation in the DAP12 gene (DAP12(KI) mice) display enhanced relative contribution of AMPA. Furthermore, neurons from DAP12(KI) P0 pups cultured without microglia develop similar synaptic alterations, suggesting that a prenatal dysfunction of microglia may impact synaptic function in the adult. As we observed that DAP12(KI) microglia overexpress genes for IL1beta, IL6 and NOS2, which are inflammatory proteins, we analyzed the impact of a pharmacologically-induced prenatal inflammation on synaptic function. Maternal injection of lipopolysaccharides induced activation of microglia at birth and alteration of glutamatergic synapses in the adult offspring. Finally, neurons cultured from neonates born to inflamed mothers and cultured without microglia also displayed altered neuronal activity.<h4>Conclusion/significance</h4>Our results demonstrate that prenatal inflammation is sufficient to induce synaptic alterations with delay. We propose that these alterations triggered by prenatal activation of microglia provide a cellular basis for the neuropsychiatric defects induced by prenatal inflammation.Anne RoumierOlivier PascualCatherine BéchadeShirley WakselmanJean-Christophe PoncerEleonore RéalAntoine TrillerAlain BessisPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 7, p e2595 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anne Roumier Olivier Pascual Catherine Béchade Shirley Wakselman Jean-Christophe Poncer Eleonore Réal Antoine Triller Alain Bessis Prenatal activation of microglia induces delayed impairment of glutamatergic synaptic function.
description	<h4>Background</h4>Epidemiological studies have linked maternal infection during pregnancy to later development of neuropsychiatric disorders in the offspring. In mice, experimental inflammation during embryonic development impairs behavioral and cognitive performances in adulthood. Synaptic dysfunctions may be at the origin of cognitive impairments, however the link between prenatal inflammation and synaptic defects remains to be established.<h4>Methodology/principal findings</h4>In this study, we show that prenatal alteration of microglial function, including inflammation, induces delayed synaptic dysfunction in the adult. DAP12 is a microglial signaling protein expressed around birth, mutations of which in the human induces the Nasu-Hakola disease, characterized by early dementia. We presently report that synaptic excitatory currents in mice bearing a loss-of-function mutation in the DAP12 gene (DAP12(KI) mice) display enhanced relative contribution of AMPA. Furthermore, neurons from DAP12(KI) P0 pups cultured without microglia develop similar synaptic alterations, suggesting that a prenatal dysfunction of microglia may impact synaptic function in the adult. As we observed that DAP12(KI) microglia overexpress genes for IL1beta, IL6 and NOS2, which are inflammatory proteins, we analyzed the impact of a pharmacologically-induced prenatal inflammation on synaptic function. Maternal injection of lipopolysaccharides induced activation of microglia at birth and alteration of glutamatergic synapses in the adult offspring. Finally, neurons cultured from neonates born to inflamed mothers and cultured without microglia also displayed altered neuronal activity.<h4>Conclusion/significance</h4>Our results demonstrate that prenatal inflammation is sufficient to induce synaptic alterations with delay. We propose that these alterations triggered by prenatal activation of microglia provide a cellular basis for the neuropsychiatric defects induced by prenatal inflammation.
format	article
author	Anne Roumier Olivier Pascual Catherine Béchade Shirley Wakselman Jean-Christophe Poncer Eleonore Réal Antoine Triller Alain Bessis
author_facet	Anne Roumier Olivier Pascual Catherine Béchade Shirley Wakselman Jean-Christophe Poncer Eleonore Réal Antoine Triller Alain Bessis
author_sort	Anne Roumier
title	Prenatal activation of microglia induces delayed impairment of glutamatergic synaptic function.
title_short	Prenatal activation of microglia induces delayed impairment of glutamatergic synaptic function.
title_full	Prenatal activation of microglia induces delayed impairment of glutamatergic synaptic function.
title_fullStr	Prenatal activation of microglia induces delayed impairment of glutamatergic synaptic function.
title_full_unstemmed	Prenatal activation of microglia induces delayed impairment of glutamatergic synaptic function.
title_sort	prenatal activation of microglia induces delayed impairment of glutamatergic synaptic function.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/94994fbe8816427c814024dac0fcffad
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Prenatal activation of microglia induces delayed impairment of glutamatergic synaptic function.

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