S100B dysregulation during brain development affects synaptic SHANK protein networks via alteration of zinc homeostasis

Abstract Autism Spectrum Disorders (ASD) are caused by a combination of genetic predisposition and nongenetic factors. Among the nongenetic factors, maternal immune system activation and zinc deficiency have been proposed. Intriguingly, as a genetic factor, copy-number variations in S100B, a pro-inf...

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Autores principales:	Eleonora Daini, Simone Hagmeyer, Chiara A. De Benedictis, Joana S. Cristóvão, Martina Bodria, Aisling M. Ross, Andrea Raab, Tobias M. Boeckers, Joerg Feldmann, Cláudio M. Gomes, Michele Zoli, Antonietta Vilella, Andreas M. Grabrucker
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/e66884e838aa463eb9316b5178485c50
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spelling	oai:doaj.org-article:e66884e838aa463eb9316b5178485c502021-11-07T12:17:55ZS100B dysregulation during brain development affects synaptic SHANK protein networks via alteration of zinc homeostasis10.1038/s41398-021-01694-z2158-3188https://doaj.org/article/e66884e838aa463eb9316b5178485c502021-11-01T00:00:00Zhttps://doi.org/10.1038/s41398-021-01694-zhttps://doaj.org/toc/2158-3188Abstract Autism Spectrum Disorders (ASD) are caused by a combination of genetic predisposition and nongenetic factors. Among the nongenetic factors, maternal immune system activation and zinc deficiency have been proposed. Intriguingly, as a genetic factor, copy-number variations in S100B, a pro-inflammatory damage-associated molecular pattern (DAMP), have been associated with ASD, and increased serum S100B has been found in ASD. Interestingly, it has been shown that increased S100B levels affect zinc homeostasis in vitro. Thus, here, we investigated the influence of increased S100B levels in vitro and in vivo during pregnancy in mice regarding zinc availability, the zinc-sensitive SHANK protein networks associated with ASD, and behavioral outcomes. We observed that S100B affects the synaptic SHANK2 and SHANK3 levels in a zinc-dependent manner, especially early in neuronal development. Animals exposed to high S100B levels in utero similarly show reduced levels of free zinc and SHANK2 in the brain. On the behavioral level, these mice display hyperactivity, increased stereotypic and abnormal social behaviors, and cognitive impairment. Pro-inflammatory factors and zinc-signaling alterations converge on the synaptic level revealing a common pathomechanism that may mechanistically explain a large share of ASD cases.Eleonora DainiSimone HagmeyerChiara A. De BenedictisJoana S. CristóvãoMartina BodriaAisling M. RossAndrea RaabTobias M. BoeckersJoerg FeldmannCláudio M. GomesMichele ZoliAntonietta VilellaAndreas M. GrabruckerNature Publishing GrouparticleNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENTranslational Psychiatry, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Eleonora Daini Simone Hagmeyer Chiara A. De Benedictis Joana S. Cristóvão Martina Bodria Aisling M. Ross Andrea Raab Tobias M. Boeckers Joerg Feldmann Cláudio M. Gomes Michele Zoli Antonietta Vilella Andreas M. Grabrucker S100B dysregulation during brain development affects synaptic SHANK protein networks via alteration of zinc homeostasis
description	Abstract Autism Spectrum Disorders (ASD) are caused by a combination of genetic predisposition and nongenetic factors. Among the nongenetic factors, maternal immune system activation and zinc deficiency have been proposed. Intriguingly, as a genetic factor, copy-number variations in S100B, a pro-inflammatory damage-associated molecular pattern (DAMP), have been associated with ASD, and increased serum S100B has been found in ASD. Interestingly, it has been shown that increased S100B levels affect zinc homeostasis in vitro. Thus, here, we investigated the influence of increased S100B levels in vitro and in vivo during pregnancy in mice regarding zinc availability, the zinc-sensitive SHANK protein networks associated with ASD, and behavioral outcomes. We observed that S100B affects the synaptic SHANK2 and SHANK3 levels in a zinc-dependent manner, especially early in neuronal development. Animals exposed to high S100B levels in utero similarly show reduced levels of free zinc and SHANK2 in the brain. On the behavioral level, these mice display hyperactivity, increased stereotypic and abnormal social behaviors, and cognitive impairment. Pro-inflammatory factors and zinc-signaling alterations converge on the synaptic level revealing a common pathomechanism that may mechanistically explain a large share of ASD cases.
format	article
author	Eleonora Daini Simone Hagmeyer Chiara A. De Benedictis Joana S. Cristóvão Martina Bodria Aisling M. Ross Andrea Raab Tobias M. Boeckers Joerg Feldmann Cláudio M. Gomes Michele Zoli Antonietta Vilella Andreas M. Grabrucker
author_facet	Eleonora Daini Simone Hagmeyer Chiara A. De Benedictis Joana S. Cristóvão Martina Bodria Aisling M. Ross Andrea Raab Tobias M. Boeckers Joerg Feldmann Cláudio M. Gomes Michele Zoli Antonietta Vilella Andreas M. Grabrucker
author_sort	Eleonora Daini
title	S100B dysregulation during brain development affects synaptic SHANK protein networks via alteration of zinc homeostasis
title_short	S100B dysregulation during brain development affects synaptic SHANK protein networks via alteration of zinc homeostasis
title_full	S100B dysregulation during brain development affects synaptic SHANK protein networks via alteration of zinc homeostasis
title_fullStr	S100B dysregulation during brain development affects synaptic SHANK protein networks via alteration of zinc homeostasis
title_full_unstemmed	S100B dysregulation during brain development affects synaptic SHANK protein networks via alteration of zinc homeostasis
title_sort	s100b dysregulation during brain development affects synaptic shank protein networks via alteration of zinc homeostasis
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/e66884e838aa463eb9316b5178485c50
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S100B dysregulation during brain development affects synaptic SHANK protein networks via alteration of zinc homeostasis

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