Disruption of melatonin synthesis is associated with impaired 14-3-3 and miR-451 levels in patients with autism spectrum disorders

Abstract Autism spectrum disorders (ASD) are characterized by a wide genetic and clinical heterogeneity. However, some biochemical impairments, including decreased melatonin (crucial for circadian regulation) and elevated platelet N-acetylserotonin (the precursor of melatonin) have been reported as...

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Autores principales:	Cécile Pagan, Hany Goubran-Botros, Richard Delorme, Marion Benabou, Nathalie Lemière, Kerren Murray, Frédérique Amsellem, Jacques Callebert, Pauline Chaste, Stéphane Jamain, Fabien Fauchereau, Guillaume Huguet, Erik Maronde, Marion Leboyer, Jean-Marie Launay, Thomas Bourgeron
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f46cefc850c64dbfa6f36f39d8a0b82c
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spelling	oai:doaj.org-article:f46cefc850c64dbfa6f36f39d8a0b82c2021-12-02T15:05:27ZDisruption of melatonin synthesis is associated with impaired 14-3-3 and miR-451 levels in patients with autism spectrum disorders10.1038/s41598-017-02152-x2045-2322https://doaj.org/article/f46cefc850c64dbfa6f36f39d8a0b82c2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02152-xhttps://doaj.org/toc/2045-2322Abstract Autism spectrum disorders (ASD) are characterized by a wide genetic and clinical heterogeneity. However, some biochemical impairments, including decreased melatonin (crucial for circadian regulation) and elevated platelet N-acetylserotonin (the precursor of melatonin) have been reported as very frequent features in individuals with ASD. To address the mechanisms of these dysfunctions, we investigated melatonin synthesis in post-mortem pineal glands - the main source of melatonin (9 patients and 22 controls) - and gut samples - the main source of serotonin (11 patients and 13 controls), and in blood platelets from 239 individuals with ASD, their first-degree relatives and 278 controls. Our results elucidate the enzymatic mechanism for melatonin deficit in ASD, involving a reduction of both enzyme activities contributing to melatonin synthesis (AANAT and ASMT), observed in the pineal gland as well as in gut and platelets of patients. Further investigations suggest new, post-translational (reduced levels of 14-3-3 proteins which regulate AANAT and ASMT activities) and post-transcriptional (increased levels of miR-451, targeting 14-3-3ζ) mechanisms to these impairments. This study thus gives insights into the pathophysiological pathways involved in ASD.Cécile PaganHany Goubran-BotrosRichard DelormeMarion BenabouNathalie LemièreKerren MurrayFrédérique AmsellemJacques CallebertPauline ChasteStéphane JamainFabien FauchereauGuillaume HuguetErik MarondeMarion LeboyerJean-Marie LaunayThomas BourgeronNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Cécile Pagan Hany Goubran-Botros Richard Delorme Marion Benabou Nathalie Lemière Kerren Murray Frédérique Amsellem Jacques Callebert Pauline Chaste Stéphane Jamain Fabien Fauchereau Guillaume Huguet Erik Maronde Marion Leboyer Jean-Marie Launay Thomas Bourgeron Disruption of melatonin synthesis is associated with impaired 14-3-3 and miR-451 levels in patients with autism spectrum disorders
description	Abstract Autism spectrum disorders (ASD) are characterized by a wide genetic and clinical heterogeneity. However, some biochemical impairments, including decreased melatonin (crucial for circadian regulation) and elevated platelet N-acetylserotonin (the precursor of melatonin) have been reported as very frequent features in individuals with ASD. To address the mechanisms of these dysfunctions, we investigated melatonin synthesis in post-mortem pineal glands - the main source of melatonin (9 patients and 22 controls) - and gut samples - the main source of serotonin (11 patients and 13 controls), and in blood platelets from 239 individuals with ASD, their first-degree relatives and 278 controls. Our results elucidate the enzymatic mechanism for melatonin deficit in ASD, involving a reduction of both enzyme activities contributing to melatonin synthesis (AANAT and ASMT), observed in the pineal gland as well as in gut and platelets of patients. Further investigations suggest new, post-translational (reduced levels of 14-3-3 proteins which regulate AANAT and ASMT activities) and post-transcriptional (increased levels of miR-451, targeting 14-3-3ζ) mechanisms to these impairments. This study thus gives insights into the pathophysiological pathways involved in ASD.
format	article
author	Cécile Pagan Hany Goubran-Botros Richard Delorme Marion Benabou Nathalie Lemière Kerren Murray Frédérique Amsellem Jacques Callebert Pauline Chaste Stéphane Jamain Fabien Fauchereau Guillaume Huguet Erik Maronde Marion Leboyer Jean-Marie Launay Thomas Bourgeron
author_facet	Cécile Pagan Hany Goubran-Botros Richard Delorme Marion Benabou Nathalie Lemière Kerren Murray Frédérique Amsellem Jacques Callebert Pauline Chaste Stéphane Jamain Fabien Fauchereau Guillaume Huguet Erik Maronde Marion Leboyer Jean-Marie Launay Thomas Bourgeron
author_sort	Cécile Pagan
title	Disruption of melatonin synthesis is associated with impaired 14-3-3 and miR-451 levels in patients with autism spectrum disorders
title_short	Disruption of melatonin synthesis is associated with impaired 14-3-3 and miR-451 levels in patients with autism spectrum disorders
title_full	Disruption of melatonin synthesis is associated with impaired 14-3-3 and miR-451 levels in patients with autism spectrum disorders
title_fullStr	Disruption of melatonin synthesis is associated with impaired 14-3-3 and miR-451 levels in patients with autism spectrum disorders
title_full_unstemmed	Disruption of melatonin synthesis is associated with impaired 14-3-3 and miR-451 levels in patients with autism spectrum disorders
title_sort	disruption of melatonin synthesis is associated with impaired 14-3-3 and mir-451 levels in patients with autism spectrum disorders
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/f46cefc850c64dbfa6f36f39d8a0b82c
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Disruption of melatonin synthesis is associated with impaired 14-3-3 and miR-451 levels in patients with autism spectrum disorders

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