Decreased phenol sulfotransferase activities associated with hyperserotonemia in autism spectrum disorders.
Journal
Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664
Informations de publication
Date de publication:
07 01 2021
07 01 2021
Historique:
received:
16
03
2020
accepted:
27
10
2020
revised:
29
09
2020
entrez:
8
1
2021
pubmed:
9
1
2021
medline:
22
6
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33414449
doi: 10.1038/s41398-020-01125-5
pii: 10.1038/s41398-020-01125-5
pmc: PMC7791095
doi:
Substances chimiques
Serotonin
333DO1RDJY
Sulfotransferases
EC 2.8.2.-
Arylsulfotransferase
EC 2.8.2.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
23Subventions
Organisme : Agence Nationale de la Recherche (French National Research Agency)
ID : ANR-10-LABX-0013
Pays : International
Références
Cancer Epidemiol Biomarkers Prev. 2004 Feb;13(2):270-6
pubmed: 14973106
FEBS Lett. 2001 Feb 9;490(1-2):39-43
pubmed: 11172807
J Pediatr. 1961 Mar;58:315-20
pubmed: 13747230
Nature. 2016 Aug 11;536(7615):205-9
pubmed: 27487209
Cytogenet Genome Res. 2008;123(1-4):205-10
pubmed: 19287157
Biol Psychiatry. 1999 Aug 1;46(3):420-4
pubmed: 10435209
Can J Physiol Pharmacol. 1981 Mar;59(3):300-6
pubmed: 6939469
Clin Chim Acta. 1993 Nov 30;221(1-2):143-58
pubmed: 7512001
J Biol Chem. 2019 Feb 15;294(7):2293-2301
pubmed: 30545938
Endocr Res. 1985;11(3-4):225-32
pubmed: 3869101
J Clin Invest. 2008 Apr;118(4):1544-52
pubmed: 18317590
J Clin Endocrinol Metab. 2001 Jun;86(6):2734-42
pubmed: 11397879
Neuropsychobiology. 1988;20(1):1-11
pubmed: 2466221
Fed Proc. 1986 Jul;45(8):2247-53
pubmed: 3459671
Thromb Res. 1987 Feb 1;45(3):279-84
pubmed: 3477882
J Lab Clin Med. 1988 Dec;112(6):773-83
pubmed: 3193032
Xenobiotica. 2016 Jul;46(7):612-619
pubmed: 26577053
Nat Genet. 2019 Mar;51(3):431-444
pubmed: 30804558
Clin Genet. 2003 Sep;64(3):190-7
pubmed: 12919132
Neuroscience. 2016 May 3;321:24-41
pubmed: 26577932
J Neural Transm (Vienna). 2018 Nov;125(11):1553-1566
pubmed: 30259128
J Am Acad Child Adolesc Psychiatry. 2004 Apr;43(4):491-9
pubmed: 15187810
Carcinogenesis. 2011 Nov;32(11):1734-40
pubmed: 21900212
Kidney Int. 1998 May;53(5):1348-52
pubmed: 9573551
Proc Natl Acad Sci U S A. 2012 Apr 3;109(14):5469-74
pubmed: 22431635
Genes Brain Behav. 2011 Feb;10(1):44-56
pubmed: 20618443
Nutr Metab (Lond). 2011 Jun 08;8(1):34
pubmed: 21651783
Arch Gen Psychiatry. 1977 May;34(5):553-6
pubmed: 558741
Neuropsychobiology. 1998;38(1):1-5
pubmed: 9701715
Proc Natl Acad Sci U S A. 2012 Mar 27;109(13):5052-6
pubmed: 22411800
J Autism Dev Disord. 1987 Sep;17(3):333-47
pubmed: 3654486
Neurochem Int. 2016 Oct 27;:
pubmed: 27984170
Nature. 2019 Mar;567(7749):535-539
pubmed: 30867594
Behav Brain Res. 2012 Mar 17;228(2):247-53
pubmed: 22101175
Protein Sci. 2018 Jan;27(1):233-244
pubmed: 28940711
Nat Neurosci. 2019 Feb;22(2):243-255
pubmed: 30617258
Mol Aspects Med. 2016 Oct;51:104-14
pubmed: 27418189
Nat Med. 2013 Jun;19(6):685-94
pubmed: 23744158
Transl Psychiatry. 2014 Nov 11;4:e479
pubmed: 25386956
Pharmacol Res. 2019 Feb;140:85-99
pubmed: 30009933
Biol Psychiatry. 1999 Jan 15;45(2):158-63
pubmed: 9951562
Mol Autism. 2018 Nov 26;9:60
pubmed: 30498565
Clin Chem Lab Med. 2008;46(2):219-24
pubmed: 18076349
Mol Psychiatry. 2002;7(1):67-71
pubmed: 11803447
Hum Mol Genet. 2019 Apr 1;28(7):1153-1161
pubmed: 30535103
BMC Pediatr. 2011 Dec 12;11:111
pubmed: 22151477
Nature. 2010 Jul 15;466(7304):368-72
pubmed: 20531469
Environ Health Perspect. 2019 Apr;127(4):46001
pubmed: 30942615
Behav Brain Res. 2013 Apr 15;243:138-45
pubmed: 23318464
J Neurosci Res. 2017 Oct;95(10):1965-1972
pubmed: 28151561
Nutrients. 2018 Mar 17;10(3):
pubmed: 29562612
Int J Dev Neurosci. 2005 Apr-May;23(2-3):171-82
pubmed: 15749243
Nature. 2007 Apr 26;446(7139):1030-7
pubmed: 17460664
Carcinogenesis. 2014 Apr;35(4):935-41
pubmed: 24318996
Sci Rep. 2017 May 18;7(1):2096
pubmed: 28522826
FASEB J. 1997 May;11(6):404-18
pubmed: 9194521
Mutat Res. 2001 Oct 1;482(1-2):27-40
pubmed: 11535246
Pharmacogenetics. 2000 Dec;10(9):789-97
pubmed: 11191883
Nature. 2009 May 28;459(7246):528-33
pubmed: 19404256
Hum Exp Toxicol. 1996 Jul;15(7):547-55
pubmed: 8818707
J Biol Chem. 2003 May 2;278(18):16315-9
pubmed: 12601002
J Pineal Res. 2005 Oct;39(3):276-82
pubmed: 16150108
Nat Rev Neurosci. 2015 Sep;16(9):551-63
pubmed: 26289574
Toxicol Sci. 2006 Mar;90(1):5-22
pubmed: 16322073
Drug Metab Dispos. 2001 Mar;29(3):274-81
pubmed: 11181495
Cell. 2018 Sep 6;174(6):1450-1464.e23
pubmed: 30100184
Drug Metab Dispos. 2012 Aug;40(8):1588-95
pubmed: 22593037
J Clin Chem Clin Biochem. 1986 Dec;24(12):1029-32
pubmed: 3546585
Metab Brain Dis. 2016 Apr;31(2):273-8
pubmed: 26464064
J Steroid Biochem Mol Biol. 2017 Nov;174:169-175
pubmed: 28867356
PLoS One. 2012;7(11):e48975
pubmed: 23139830
JAMA Psychiatry. 2019 Oct 1;76(10):1035-1043
pubmed: 31314057
Dev Med Child Neurol. 2018 May;60(5):445-451
pubmed: 29574884
Neural Dev. 2016 Apr 18;11:11
pubmed: 27089953
Drug Metab Dispos. 2009 Apr;37(4):706-9
pubmed: 19171676
J Agric Food Chem. 2004 Jun 30;52(13):4139-43
pubmed: 15212460
Life Sci. 1976 Oct 15;19(8):1161-74
pubmed: 994720
Genes Brain Behav. 2008 Mar;7(2):152-63
pubmed: 17559418
Dev Pharmacol Ther. 1991;16(2):83-8
pubmed: 1914783
Eur Neuropsychopharmacol. 2014 Jun;24(6):919-29
pubmed: 24613076
Am J Hum Genet. 2005 Aug;77(2):265-79
pubmed: 15995945
Pharmgenomics Pers Med. 2013;6:19-24
pubmed: 23526707
Am J Med Genet A. 2014 Nov;164A(11):2753-63
pubmed: 25125150
Mol Autism. 2017 May 22;8:21
pubmed: 28540026
Neuropsychobiology. 2010;61(1):27-32
pubmed: 19923863
Front Genet. 2019 Jun 19;10:574
pubmed: 31316544
J Biol Chem. 2017 Dec 8;292(49):20305-20312
pubmed: 29038294
Biol Psychiatry. 2005 Jan 15;57(2):134-8
pubmed: 15652871