In utero exposure to endogenous maternal polyclonal anti-Caspr2 antibody leads to behavioral abnormalities resembling autism spectrum disorder in male mice

Abstract The concept that exposure in utero to maternal anti-brain antibodies contributes to the development of autism spectrum disorders (ASD) has been entertained for over a decade. We determined that antibodies targeting Caspr2 are present at high frequency in mothers with brain-reactive serology...

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Autores principales:	Ciara Bagnall-Moreau, Patricio T. Huerta, Davide Comoletti, Andrea La-Bella, Roseann Berlin, Chunfang Zhao, Bruce T. Volpe, Betty Diamond, Lior Brimberg
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0d79b86102654d0993d2e8b06b7ea1de
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spelling	oai:doaj.org-article:0d79b86102654d0993d2e8b06b7ea1de2021-12-02T19:04:25ZIn utero exposure to endogenous maternal polyclonal anti-Caspr2 antibody leads to behavioral abnormalities resembling autism spectrum disorder in male mice10.1038/s41598-020-71201-92045-2322https://doaj.org/article/0d79b86102654d0993d2e8b06b7ea1de2020-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-71201-9https://doaj.org/toc/2045-2322Abstract The concept that exposure in utero to maternal anti-brain antibodies contributes to the development of autism spectrum disorders (ASD) has been entertained for over a decade. We determined that antibodies targeting Caspr2 are present at high frequency in mothers with brain-reactive serology and a child with ASD, and further demonstrated that exposure in utero to a monoclonal anti-Caspr2 antibody, derived from a mother of an ASD child, led to an-ASD like phenotype in male offspring. Now we propose a new model to study the effects of in utero exposure to anti-Caspr2 antibody. Dams immunized with the extracellular portion of Caspr2 express anti-Caspr2 antibodies throughout gestation to better mimic the human condition. Male but not female mice born to dams harboring polyclonal anti-Caspr2 antibodies showed abnormal cortical development, decreased dendritic complexity of excitatory neurons and reduced numbers of inhibitory neurons in the hippocampus, as well as repetitive behaviors and impairments in novelty interest in the social preference test as adults. These data supporting the pathogenicity of anti-Caspr2 antibodies are consistent with the concept that anti-brain antibodies present in women during gestation can alter fetal brain development, and confirm that males are peculiarly susceptible.Ciara Bagnall-MoreauPatricio T. HuertaDavide ComolettiAndrea La-BellaRoseann BerlinChunfang ZhaoBruce T. VolpeBetty DiamondLior BrimbergNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ciara Bagnall-Moreau Patricio T. Huerta Davide Comoletti Andrea La-Bella Roseann Berlin Chunfang Zhao Bruce T. Volpe Betty Diamond Lior Brimberg In utero exposure to endogenous maternal polyclonal anti-Caspr2 antibody leads to behavioral abnormalities resembling autism spectrum disorder in male mice
description	Abstract The concept that exposure in utero to maternal anti-brain antibodies contributes to the development of autism spectrum disorders (ASD) has been entertained for over a decade. We determined that antibodies targeting Caspr2 are present at high frequency in mothers with brain-reactive serology and a child with ASD, and further demonstrated that exposure in utero to a monoclonal anti-Caspr2 antibody, derived from a mother of an ASD child, led to an-ASD like phenotype in male offspring. Now we propose a new model to study the effects of in utero exposure to anti-Caspr2 antibody. Dams immunized with the extracellular portion of Caspr2 express anti-Caspr2 antibodies throughout gestation to better mimic the human condition. Male but not female mice born to dams harboring polyclonal anti-Caspr2 antibodies showed abnormal cortical development, decreased dendritic complexity of excitatory neurons and reduced numbers of inhibitory neurons in the hippocampus, as well as repetitive behaviors and impairments in novelty interest in the social preference test as adults. These data supporting the pathogenicity of anti-Caspr2 antibodies are consistent with the concept that anti-brain antibodies present in women during gestation can alter fetal brain development, and confirm that males are peculiarly susceptible.
format	article
author	Ciara Bagnall-Moreau Patricio T. Huerta Davide Comoletti Andrea La-Bella Roseann Berlin Chunfang Zhao Bruce T. Volpe Betty Diamond Lior Brimberg
author_facet	Ciara Bagnall-Moreau Patricio T. Huerta Davide Comoletti Andrea La-Bella Roseann Berlin Chunfang Zhao Bruce T. Volpe Betty Diamond Lior Brimberg
author_sort	Ciara Bagnall-Moreau
title	In utero exposure to endogenous maternal polyclonal anti-Caspr2 antibody leads to behavioral abnormalities resembling autism spectrum disorder in male mice
title_short	In utero exposure to endogenous maternal polyclonal anti-Caspr2 antibody leads to behavioral abnormalities resembling autism spectrum disorder in male mice
title_full	In utero exposure to endogenous maternal polyclonal anti-Caspr2 antibody leads to behavioral abnormalities resembling autism spectrum disorder in male mice
title_fullStr	In utero exposure to endogenous maternal polyclonal anti-Caspr2 antibody leads to behavioral abnormalities resembling autism spectrum disorder in male mice
title_full_unstemmed	In utero exposure to endogenous maternal polyclonal anti-Caspr2 antibody leads to behavioral abnormalities resembling autism spectrum disorder in male mice
title_sort	in utero exposure to endogenous maternal polyclonal anti-caspr2 antibody leads to behavioral abnormalities resembling autism spectrum disorder in male mice
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/0d79b86102654d0993d2e8b06b7ea1de
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In utero exposure to endogenous maternal polyclonal anti-Caspr2 antibody leads to behavioral abnormalities resembling autism spectrum disorder in male mice

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