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

Scientific Reports
Cecile PaganThomas Bourgeron

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 pat...Continue Reading

References

Nov 30, 1993·Clinica Chimica Acta; International Journal of Clinical Chemistry·I P KemaF A Muskiet
Mar 1, 1961·The Journal of Pediatrics·R J SCHAIN, D X FREEDMAN
Jan 13, 2005·Proceedings of the National Academy of Sciences of the United States of America·Surajit GangulyDavid C Klein
Jan 15, 2005·Sleep Medicine Reviews·Bruno ClaustratGuy Chazot
Jan 18, 2005·Biological Psychiatry·Sylvie TordjmanYvan Touitou
Jul 9, 2005·Research in Developmental Disabilities·Kristen S L LamL Eugene Arnold
Mar 25, 2006·Endocrinology·Katrin AckermannJörg H Stehle
May 17, 2007·Molecular Psychiatry·J MelkeT Bourgeron
Oct 25, 2007·Molecular Psychiatry·C TomaUNKNOWN International Molecular Genetic Study of Autism Consortium
Jan 10, 2008·Journal of Child Neurology·Ivy M AndersenBeth A Malow
Apr 19, 2008·Cold Spring Harbor Symposia on Quantitative Biology·T Bourgeron
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Sung-Wuk JangKeqiang Ye
Aug 4, 2010·Genes & Development·Duonan YuMitchell J Weiss
May 27, 2011·Nature·Irina VoineaguDaniel H Geschwind
Aug 11, 2011·Journal of Circadian Rhythms·Daniel F KripkeJohn R Kelsoe
May 1, 2012·Free Radical Biology & Medicine·Alessandra FrustaciStefano Bonassi
Jul 11, 2012·Journal of Pineal Research·Hany Goubran BotrosThomas Bourgeron
Apr 29, 2014·American Journal of Human Genetics·Dalila PintoStephen W Scherer
Jul 26, 2014·Journal of Autism and Developmental Disorders·Olivia J VeatchBeth A Malow
May 20, 2015·Scientific Reports·Pierre Alexis GeoffroyBruno Etain
Jun 24, 2015·The Journal of Endocrinology·Jonathan D Johnston, Debra J Skene
Jul 15, 2015·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Kaya K JacobsenJan Haavik
Aug 21, 2015·Nature Reviews. Neuroscience·Thomas Bourgeron
Oct 13, 2015·Drug Discovery Today·Yasaman Aghazadeh, Vassilios Papadopoulos
Dec 30, 2015·The Journal of General Physiology·Haijie YuBertil Hille

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Citations

Jan 19, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yunho JinYonggeun Hong
Dec 20, 2017·Scientific Reports·Marion BenabouThomas Bourgeron
Sep 21, 2019·Current Pharmaceutical Design·George Anderson
Nov 5, 2019·Current Pharmaceutical Design·Luciana PinatoSanseray da Silveira Cruz-Machado
Nov 5, 2019·Current Pharmaceutical Design·George Anderson, Susana R Betancort Medina
Nov 7, 2019·Current Pharmaceutical Design·Mahesh Mundalil VasuAyyappan Anitha
Jan 17, 2019·Journal of Clinical Medicine·Alessandro TonacciSebastiano Gangemi
Feb 26, 2019·Frontiers in Endocrinology·Tal Shomrat, Nir Nesher
May 21, 2019·Egyptian Journal of Basic and Clinical Pharmacology·Abdulla Abu-Bakr Badawy
Oct 19, 2019·Research and Practice in Thrombosis and Haemostasis·Manisha PadmakumarKathleen Freson
Apr 16, 2019·Biological Research for Nursing·Ann E E JohanssonBernie Devlin
Feb 23, 2019·Frontiers in Psychiatry·Anna MaruaniRichard Delorme
Sep 19, 2019·International Journal of Environmental Research and Public Health·Anna Strunecka, Otakar Strunecky
May 24, 2018·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·Wei-Hong KuangJin Li
Dec 23, 2020·Epigenomics·Mohammad Hossein PourhanifehAzam Hosseinzadeh
Jan 10, 2021·Journal of Pineal Research·Sanseray da Silveira Cruz-MachadoLuciana Pinato
Dec 29, 2020·Journal of Pineal Research·Guillaume DumasThomas Bourgeron
Aug 4, 2019·Behavioural Brain Research·Lucie JurekMarie-Maude Geoffray
May 14, 2021·Frontiers in Pharmacology·Monika Dmitrzak-WeglarzJoanna Pawlak
Jul 18, 2021·Neuroscience and Biobehavioral Reviews·Rana FetitStephen M Lawrie
Jul 29, 2021·Epigenomics·Hamid Mostafavi AbdolmalekySam Thiagalingam
Jul 19, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Zhou-Yue WuFeng Han

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Methods Mentioned

BETA
PCR
exome sequencing
ELISA
genotyping

Software Mentioned

JMP Pro
Stata

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