Remember Me
Or use your Academic/Social account:


Or use your Academic/Social account:


You have just completed your registration at OpenAire.

Before you can login to the site, you will need to activate your account. An e-mail will be sent to you with the proper instructions.


Please note that this site is currently undergoing Beta testing.
Any new content you create is not guaranteed to be present to the final version of the site upon release.

Thank you for your patience,
OpenAire Dev Team.

Close This Message


Verify Password:
Verify E-mail:
*All Fields Are Required.
Please Verify You Are Human:
fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
Goeden, Nick; Velasquez, Juan C.; Bonnin, Alexandre (2013)
Publisher: Translational Developmental Psychiatry
Journal: Translational Developmental Psychiatry
Languages: English
Types: Article
Dysfunction of brain serotonin (5-HT) signaling contributes to the pathophysiology of several psychiatric disorders. However, before 5-HT acts as a neurotransmitter/neuromodulator in the adult brain, increasing evidence suggests that it plays crucial roles in the modulation of essential neurodevelopmental processes. It was recently demonstrated that the placenta synthesizes 5-HT from maternally derived tryptophan during pregnancy. Therefore, genetic and environmental perturbations that affect placental tryptophan metabolism could alter neurodevelopmental processes in the developing embryo, and contribute to the developmental origin of psychiatric disorders. Here we discuss how disruptions of the placental tryptophan metabolic pathway may lead to abnormal brain development and function in adult life.Keywords: placenta; serotonin; tryptophan; schizophrenia; autism; stress; fetal programming; fetal brain(Publication: 9 September 2013)Citation: Translational Developmental Psychiatry 2013, 1: 20593 - http://dx.doi.org/10.3402/tdp.v1i0.20593
  • The results below are discovered through our pilot algorithms. Let us know how we are doing!

    • 1. Nathanielsz PW. Fetal programming: from gene to functional systems - an overview. J Physiol 2003; 547: 3 4.
    • 2. Barker D, Osmond C, Golding J. Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. Br Med J 1989; 298: 564 7.
    • 3. Jansson T, Powell TL. Role of the placenta in fetal programming: underlying mechanisms and potential interventional approaches. Clin Sci 2007; 113: 1 13.
    • 4. Heindel JJ. Animal models for probing the developmental basis of disease and dysfunction paradigm. Basic Clin Pharmacol Toxicol 2008; 102: 76 81.
    • 5. Bale TL, Baram TZ, Brown AS, Goldstein JM, Insel TR, McCarthy MM et al. Early life programming and neurodevelopmental disorders. Biol Psychiatry 2010; 68: 314 9.
    • 6. Brown AS, Derkits EJ. Prenatal infection and schizophrenia: a review of epidemiologic and translational studies. Am J Psychiatry 2010; 167: 261 80.
    • 7. Brown AS. Epidemiologic studies of exposure to prenatal infection and risk of schizophrenia and autism. Dev Neurobiol 2012; 72: 1272 6.
    • 8. Zerbo O, Iosif A-M, Walker C, Ozonoff S, Hansen RL, Hertz-Picciotto I. Is maternal influenza or fever during pregnancy associated with autism or developmental delays? Results from the CHARGE (CHildhood Autism Risks from Genetics and Environment) study. J Autism Dev Disord 2013; 43: 25 33.
    • 9. Weinstock M. Intrauterine factors as determinants of depressive disorder. Isr J Psychiatry Relat Sci 2010; 47: 36 45.
    • 10. Myatt L. Placental adaptive responses and fetal programming. J Physiol 2006; 572(Pt 1): 25 30.
    • 11. Cox B, Kotlyar M, Evangelou AI, Ignatchenko V, Ignatchenko A, Whiteley K et al. Comparative systems biology of human and mouse as a tool to guide the modeling of human placental pathology. Mol Syst Biol 2009; 5: 279.
    • 12. Roberts JM, Gammill HS. Preeclampsia: recent insights. Hypertension 2005; 46: 1243 9.
    • 13. Mari G, Hanif F. Intrauterine growth restriction: how to manage and when to deliver. Clin Obstet Gynecol 2007; 50: 497 509.
    • 14. Rees S, Harding R, Walker D. The biological basis of injury and neuroprotection in the fetal and neonatal brain. Int J Dev Neurosci 2011; 29: 551 63.
    • 15. Nicoletto SF, Rinaldi A. In the womb's shadow. The theory of prenatal programming as the fetal origin of various adult diseases is increasingly supported by a wealth of evidence. EMBO Rep 2011; 12: 30 4.
    • 16. Bonnin A, Goeden N, Chen K, Wilson ML, King J, Shih JC et al. A transient placental source of serotonin for the fetal forebrain. Nature 2011; 472: 347 50.
    • 17. Bonnin A, Torii M, Wang L, Rakic P, Levitt P. Serotonin modulates the response of embryonic thalamocortical axons to netrin-1. Nat Neurosci 2007; 10: 588 97.
    • 18. Gaspar P, Cases O, Maroteaux L. The developmental role of serotonin: news from mouse molecular genetics. Nat Rev Neurosci 2003; 4: 1002 12.
    • 19. Janusonis S, Gluncic V, Rakic P. Early serotonergic projections to Cajal-Retzius cells: relevance for cortical development. J Neurosci 2004; 24: 1652 9.
    • 20. McIlvain VA, Robertson DR, Maimone MM, McCasland JS. Abnormal thalamocortical pathfinding and terminal arbors lead to enlarged barrels in neonatal GAP-43 heterozygous mice. J Comp Neurol 2003; 462: 252 64.
    • 21. Vitalis T, Parnavelas JG. The role of serotonin in early cortical development. Dev Neurosci 2003; 25: 245 56.
    • 22. Ansorge MS, Zhou M, Lira A, Hen R, Gingrich JA. Early-life blockade of the 5-HT transporter alters emotional behavior in adult mice. Science 2004; 306: 879 81.
    • 23. Bonnin A, Levitt P. Fetal, maternal, and placental sources of serotonin and new implications for developmental programming of the brain. Neuroscience 2011; 197: 1 7.
    • 24. Bonnin A, Levitt P. Placental source for 5-HT that tunes fetal brain development. Neuropsychopharmacol 2012; 37: 299 300.
    • 25. DubeĀ“ F, Amireault P. Local serotonergic signaling in mammalian follicles, oocytes and early embryos. Life Sci 2007; 81: 1627 37.
    • 26. Goeden N, Bonnin A. Ex vivo perfusion of mid-to-lategestation mouse placenta for maternal-fetal interaction studies during pregnancy. Nat Protoc 2012; 8: 66 74.
    • 27. Daneman R, Zhou L, Kebede AA, Barres BA. Pericytes are required for blood-brain barrier integrity during embryogenesis. Nature 2010; 468: 562 6.
    • 28. Bonnin A, Peng W, Hewlett W, Levitt P. Expression mapping of 5-HT1 serotonin receptor subtypes during fetal and early postnatal mouse forebrain development. Neuroscience 2006; 141: 781 94.
    • 29. Peters DA. Effects of maternal stress during different gestational periods on the serotonergic system in adult rat offspring. Pharmacol Biochem Behav 1988; 31: 839 43.
    • 30. Peters DAV. Both prenatal and postnatal factors contribute to the effects of maternal stress on offspring behavior and central 5-hydroxytryptamine receptors in the rat. Pharmacol Biochem Behav 1988; 30: 669 73.
    • 31. Peters DA. Maternal stress increases fetal brain and neonatal cerebral cortex 5-hydroxytryptamine synthesis in rats: a possible mechanism by which stress influences brain development. Pharmacol Biochem Behav 1990; 35: 943 7.
    • 32. Jauniaux E, Sherwood RA, Jurkovic D, Boa FG, Campbell S. Amino acid concentrations in human embryological fluids. Hum Reprod 1994; 9: 1175 9.
    • 33. Oberlander TF, Gingrich JA, Ansorge MS. Sustained neurobehavioral effects of exposure to SSRI antidepressants during development: molecular to clinical evidence. Clin Pharmacol Ther 2009; 86: 672 7.
    • 34. Suzuki S, ToneĀ“ S, Takikawa O, Kubo T, Kohno I, Minatogawa Y. Expression of indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase in early concepti. Biochem J 2001; 355(Pt 2): 425 9.
    • 35. Kanai M, Funakoshi H, Takahashi H, Hayakawa T, Mizuno S, Matsumoto K et al. Tryptophan 2,3-dioxygenase is a key modulator of physiological neurogenesis and anxiety-related behavior in mice. Mol Brain 2009; 2: 8.
    • 36. Nabi R, Serajee FJ, Chugani DC, Zhong H, Huq AH. Association of tryptophan 2,3 dioxygenase gene polymorphism with autism. Am J Med Genet 2004; 125B: 63 8.
    • 37. Miller CL, Murakami P, Ruczinski I, Ross RG, Sinkus M, Sullivan B et al. Two complex genotypes relevant to the kynurenine pathway and melanotropin function show association with schizophrenia and bipolar disorder. Schizophr Res 2009; 113: 259 67.
  • No related research data.
  • No similar publications.

Share - Bookmark

Download from

Cite this article

Collected from