Keck School Faculty

Alexandre Bonnin

Alexandre Bonnin

Associate Professor of Physiology and Neuroscience
Medicine
ZNI 421, 1501 San Pablo Street Health Sciences Campus Los Angeles

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Brain & Behavior Research Foundation (NARSAD): Daniel X. Freedman Award for outstanding basic research achievement , 2011

Brain & Behavior Research Foundation (NARSAD): Daniel X. Freedman Award for outstanding basic research achievement, 2011

Prenatal disruption of blood-brain barrier formation via cyclooxygenase activation leads to lifelong brain inflammation Proc Natl Acad Sci U S A. 2022 04 12; 119(15):e2113310119. . View in PubMed

In utero exposure to maternal anti-aquaporin-4 antibodies alters brain vasculature and neural dynamics in male mouse offspring Sci Transl Med. 2022 04 20; 14(641):eabe9726. . View in PubMed

Correction to "In Utero Exposure to Citalopram Mitigates Maternal Stress Effects on Fetal Brain Development" ACS Chem Neurosci. 2020 Feb 05; 11(3):484. . View in PubMed

Serotonin homeostasis in the materno-foetal interface at term: Role of transporters (SERT/SLC6A4 and OCT3/SLC22A3) and monoamine oxidase A (MAO-A) in uptake and degradation of serotonin by human and rat term placenta Acta Physiol (Oxf). 2020 08; 229(4):e13478. . View in PubMed

In Utero Exposure to Citalopram Mitigates Maternal Stress Effects on Fetal Brain Development ACS Chem Neurosci. 2019 07 17; 10(7):3307-3317. . View in PubMed

Long term effects of neonatal exposure to fluoxetine on energy balance: A systematic review of experimental studies Eur J Pharmacol. 2018 Aug 15; 833:298-306. . View in PubMed

Asian Zika virus strains target CD14+ blood monocytes and induce M2-skewed immunosuppression during pregnancy Nat Microbiol. 2017 Nov; 2(11):1558-1570. . View in PubMed

Impact of Maternal Serotonin Transporter Genotype on Placental Serotonin, Fetal Forebrain Serotonin, and Neurodevelopment Neuropsychopharmacology. 2017 01; 42(2):427-436. . View in PubMed

Effect of Maternal ±Citalopram Exposure on P11 Expression and Neurogenesis in the Mouse Fetal Brain ACS Chem Neurosci. 2017 05 17; 8(5):1019-1025. . View in PubMed

Prenatal Dynamics of Kynurenine Pathway Metabolism in Mice: Focus on Kynurenic Acid Dev Neurosci. 2017; 39(6):519-528. . View in PubMed

A Placenta-Specific Genetic Manipulation Reprograms Offspring Brain Development and Function Biol Psychiatry. 2017 07 15; 82(2):81-82. . View in PubMed

ACS Chem Neurosci. 2016 Mar 16; 7(3):327-38. . View in PubMed

Maternal Inflammation Disrupts Fetal Neurodevelopment via Increased Placental Output of Serotonin to the Fetal Brain J Neurosci. 2016 06 01; 36(22):6041-9. . View in PubMed

Maternal and offspring pools of osteocalcin influence brain development and functions Cell. 2013 Sep 26; 155(1):228-41. . View in PubMed

Placental serotonin: implications for the developmental effects of SSRIs and maternal depression Front Cell Neurosci. 2013; 7:47. . View in PubMed

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

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

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

Placental source for 5-HT that tunes fetal brain development Neuropsychopharmacology. 2012 Jan; 37(1):299-300. . View in PubMed

Fetal, maternal, and placental sources of serotonin and new implications for developmental programming of the brain Neuroscience. 2011 Dec 01; 197:1-7. . View in PubMed

A transient placental source of serotonin for the fetal forebrain Nature. 2011 Apr 21; 472(7343):347-50. . View in PubMed

Serotonin modulates the response of embryonic thalamocortical axons to netrin-1 Nat Neurosci. 2007 May; 10(5):588-97. . View in PubMed

Region- and age-specific deficits in gamma-aminobutyric acidergic neuron development in the telencephalon of the uPAR(-/-) mouse J Comp Neurol. 2005 Sep 05; 489(4):449-66. . View in PubMed

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

Progenitor cells of the olfactory receptor neuron lineage Microsc Res Tech. 2002 Aug 01; 58(3):176-88. . View in PubMed

Research Topics
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

Research Overview
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.
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