1. Fetal programming of adult mental disorders
2. Influence of placental metabolism on fetal brain development
3. Role of serotonin (5-HT) in fetal programming of adult diseases
Our goal is to understand how maternal-fetal interactions affect fetal brain development. The current focus is on the role of serotonin (5-HT) signaling in fetal programming or in other words, how serotonin signaling affects the mechanisms by which maternal and environmental factors shape the fetal brain and influence the development of adult diseases. These studies should ultimately provide new clues into the developmental origin of several mental health-related disorders in humans, such as autism and schizophrenia.
These and other disorders of adult brain function have developmental components suggesting a crucial ontogenetic role of neurotransmitter systems. In particular the serotonergic modulation of axon guidance mechanisms is important for the refinement of neuronal circuits? formation in utero, suggesting that serotonergic signaling is important for normal fetal brain wiring.
We are currently investigating how maternal/environmental factors affect the serotonergic modulation of fetal brain development; factors that alter 5-HT availability in the maternal and/or fetal compartments (e.g. maternal/placental metabolism, infections, stress, exposure to therapeutic drugs) can potentially alter fetal brain wiring and function in the embryo. We developed a new technology to study the molecular, neurochemical and metabolic details of the maternal-fetal interaction in the mouse. This technology will enable us to test how changes in placental metabolism at different stages of gestation impact the supply of 5-HT and other molecules to the fetus and ultimately fetal brain wiring in utero. This will provide unique opportunities to determine how maternal and placental derived neurotransmitters, cytokines and hormones impact the development of 5-HT-relevant and other circuits that have been implicated in neurodevelopmental disorders. We are also pursuing a translational approach aiming at understanding and potentially reducing the effects of therapeutic drugs, in particular antidepressants, on fetal brain development.
Brain & Behavior Research Foundation (NARSAD): Daniel X. Freedman Award for outstanding basic research achievement , 2011
King JR, Velasquez JC, Torii M, Bonnin A. Effect of Maternal ±Citalopram Exposure on P11 Expression and Neurogenesis in the Mouse Fetal Brain. ACS Chem Neurosci. 2017 Jan 13. View in: PubMed
Muller CL, Anacker AM, Rogers TD, Goeden N, Keller EH, Forsberg CG, Kerr TM, Wender C, Anderson GM, Stanwood GD, Blakely RD, Bonnin A, Veenstra-VanderWeele J. Impact of Maternal Serotonin Transporter Genotype on Placental Serotonin, Fetal Forebrain Serotonin, and Neurodevelopment. Neuropsychopharmacology. 2017 Jan; 42(2):427-436. View in: PubMed
Goeden N, Velasquez J, Arnold KA, Chan Y, Lund BT, Anderson GM, Bonnin A. Maternal Inflammation Disrupts Fetal Neurodevelopment via Increased Placental Output of Serotonin to the Fetal Brain. J Neurosci. 2016 Jun 1; 36(22):6041-9. View in: PubMed
Velasquez JC, Goeden N, Herod SM, Bonnin A. Maternal Pharmacokinetics and Fetal Disposition of (±)-Citalopram during Mouse Pregnancy. ACS Chem Neurosci. 2016 Jan 30. View in: PubMed
Oury F, Khrimian L, Denny CA, Gardin A, Chamouni A, Goeden N, Huang YY, Lee H, Srinivas P, Gao XB, Suyama S, Langer T, Mann JJ, Horvath TL, Bonnin A, Karsenty G. Maternal and offspring pools of osteocalcin influence brain development and functions. Cell. 2013 Sep 26; 155(1):228-41. View in: PubMed
Goeden N, Bonnin A. Ex vivo perfusion of mid-to-late-gestation mouse placenta for maternal-fetal interaction studies during pregnancy. Nat Protoc. 2013 Jan; 8(1):66-74. View in: PubMed
Velasquez JC, Goeden N, Bonnin A. Placental serotonin: implications for the developmental effects of SSRIs and maternal depression. Front Cell Neurosci. 2013; 7:47. View in: PubMed
Bonnin A, Zhang L, Blakely RD, Levitt P. The SSRI Citalopram Affects Fetal Thalamic Axon Responsiveness to Netrin-1 In vitro Independently of SERT Antagonism. Neuropsychopharmacology. 2012 Jul; 37(8):1879-84. View in: PubMed
van Kleef ES, Gaspar P, Bonnin A. Insights into the complex influence of 5-HT signaling on thalamocortical axonal system development. Eur J Neurosci. 2012 May; 35(10):1563-72. View in: PubMed
Bonnin A, Levitt P. Placental Source for 5-HT that Tunes Fetal Brain Development. Neuropsychopharmacology. 2012 Jan; 37(1):299-300. View in: PubMed
Bonnin A, Levitt P. Fetal, maternal, and placental sources of serotonin and new implications for developmental programming of the brain. Neuroscience. 2011 Dec 1; 197:1-7. View in: PubMed
Bonnin A, Goeden N, Chen K, Wilson ML, King J, Shih JC, Blakely RD, Deneris ES, Levitt P. A transient placental source of serotonin for the fetal forebrain. Nature. 2011 Apr 21; 472(7343):347-50. View in: PubMed
Bonnin A, Torii M, Wang L, Rakic P, Levitt P. Serotonin modulates the response of embryonic thalamocortical axons to netrin-1. Nat Neurosci. 2007 May; 10(5):588-97. View in: PubMed
Eagleson KL, Bonnin A, Levitt P. Region- and age-specific deficits in gamma-aminobutyric acidergic neuron development in the telencephalon of the uPAR(-/-) mouse. J Comp Neurol. 2005 Sep 5; 489(4):449-66. View in: PubMed
Kawauchi S, Beites CL, Crocker CE, Wu HH, Bonnin A, Murray R, Calof AL. Molecular signals regulating proliferation of stem and progenitor cells in mouse olfactory epithelium. Dev Neurosci. 2004 Mar-Aug; 26(2-4):166-80. View in: PubMed
Calof AL, Bonnin A, Crocker C, Kawauchi S, Murray RC, Shou J, Wu HH. Progenitor cells of the olfactory receptor neuron lineage. Microsc Res Tech. 2002 Aug 1; 58(3):176-88. View in: PubMed