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Decreased phenol sulfotransferase activities associated with hyperserotonemia in autism spectrum disorders.
Pagan, Cécile; Benabou, Marion; Leblond, Claire; Cliquet, Freddy; Mathieu, Alexandre; Lemière, Nathalie; Goubran-Botros, Hany; Delorme, Richard; Leboyer, Marion; Callebert, Jacques; Bourgeron, Thomas; Launay, Jean-Marie.
Afiliación
  • Pagan C; Service de Biochimie et Biologie Moléculaire, INSERM U942, Hôpital Lariboisière, AP-HP, Paris, France.
  • Benabou M; Fondation Fondamental, Créteil, France.
  • Leblond C; Human Genetics and Cognitive Functions Unit, Institut Pasteur, UMR 3571, CNRS, Université de Paris, Ecole Doctorale Bio Sorbonne Paris Cité, Paris, 75015, France.
  • Cliquet F; Université de Paris, Paris, France.
  • Mathieu A; Service de Biochimie et Biologie Moléculaire, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, 69500, Bron, France.
  • Lemière N; Human Genetics and Cognitive Functions Unit, Institut Pasteur, UMR 3571, CNRS, Université de Paris, Ecole Doctorale Bio Sorbonne Paris Cité, Paris, 75015, France.
  • Goubran-Botros H; Human Genetics and Cognitive Functions Unit, Institut Pasteur, UMR 3571, CNRS, Université de Paris, Ecole Doctorale Bio Sorbonne Paris Cité, Paris, 75015, France.
  • Delorme R; Human Genetics and Cognitive Functions Unit, Institut Pasteur, UMR 3571, CNRS, Université de Paris, Ecole Doctorale Bio Sorbonne Paris Cité, Paris, 75015, France.
  • Leboyer M; Human Genetics and Cognitive Functions Unit, Institut Pasteur, UMR 3571, CNRS, Université de Paris, Ecole Doctorale Bio Sorbonne Paris Cité, Paris, 75015, France.
  • Callebert J; Human Genetics and Cognitive Functions Unit, Institut Pasteur, UMR 3571, CNRS, Université de Paris, Ecole Doctorale Bio Sorbonne Paris Cité, Paris, 75015, France.
  • Bourgeron T; Human Genetics and Cognitive Functions Unit, Institut Pasteur, UMR 3571, CNRS, Université de Paris, Ecole Doctorale Bio Sorbonne Paris Cité, Paris, 75015, France.
  • Launay JM; Fondation Fondamental, Créteil, France.
Transl Psychiatry ; 11(1): 23, 2021 01 07.
Article en En | MEDLINE | ID: mdl-33414449
Hyperserotonemia is the most replicated biochemical abnormality associated with autism spectrum disorders (ASD). However, previous studies of serotonin synthesis, catabolism, and transport have not elucidated the mechanisms underlying this hyperserotonemia. Here we investigated serotonin sulfation by phenol sulfotransferases (PST) in blood samples from 97 individuals with ASD and their first-degree relatives (138 parents and 56 siblings), compared with 106 controls. We report a deficient activity of both PST isoforms (M and P) in platelets from individuals with ASD (35% and 78% of patients, respectively), confirmed in autoptic tissues (9 pineal gland samples from individuals with ASD-an important source of serotonin). Platelet PST-M deficiency was strongly associated with hyperserotonemia in individuals with ASD. We then explore genetic or pharmacologic modulation of PST activities in mice: variations of PST activities were associated with marked variations of blood serotonin, demonstrating the influence of the sulfation pathway on serotonemia. We also conducted in 1645 individuals an extensive study of SULT1A genes, encoding PST and mapping at highly polymorphic 16p11.2 locus, which did not reveal an association between copy number or single nucleotide variations and PST activity, blood serotonin or the risk of ASD. In contrast, our broader assessment of sulfation metabolism in ASD showed impairments of other sulfation-related markers, including inorganic sulfate, heparan-sulfate, and heparin sulfate-sulfotransferase. Our study proposes for the first time a compelling mechanism for hyperserotonemia, in a context of global impairment of sulfation metabolism in ASD.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastorno del Espectro Autista Tipo de estudio: Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Transl Psychiatry Año: 2021 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastorno del Espectro Autista Tipo de estudio: Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Transl Psychiatry Año: 2021 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos