Alexandre Bonnin, PhD

Title(s)Associate Professor of Pathology
SchoolKeck School of Medicine of Usc
AddressZNI 421, 1501 San Pablo Street
Off Campus
Los Angeles CA 90033
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    Collapse Biography 
    Collapse Awards and Honors
    Brain & Behavior Research Foundation (NARSAD)2011Daniel X. Freedman Award for outstanding basic research achievement

    Collapse Overview 
    Collapse Overview
    A. Main projects:
    Research in the Bonnin's lab focuses on understanding how maternal-fetal interactions shape fetal brain development during pregnancy; the goal is to identify molecular and cellular mechanism by which prenatal insults influence normal brain development leading to the emergence of mental disorders later in the offspring life.
    Our two main projects aim at understanding the mechanisms by which prenatal stress and maternal immune activation (MIA), such as in response to viral infection, affect fetal brain development; two prenatal insults that are known risk factors for neurological disorders later in the offspring life.

    A hallmark of gestational MIA is the chronic activation of microglial cells and neuroinflammation in the adult offspring brain. These are phenotypes also observed after blood-brain barrier (BBB) lesions in adults. We recently demonstrated that gestational MIA directly impacts BBB development in utero and BBB function across the lifespan, leading to chronic neuroinflammation and altered brain function (a). These observations support the idea that prenatal inflammation and subsequent activation of the microglia in early life disrupts BBB formation, leading to BBB breakdown across the lifespan. This self-perpetuating cycle of BBB breakdown and brain inflammation would ultimately promote increased risk for aging-related neuropathology later in life. We currently investigate this novel mechanism using pharmacological and genetic tools.
    Our approaches explore vastly understudied life-long mechanisms involved in the etiology of vascular contributions to cognitive impairment and dementia, providing insights into the developmental origins of devastating diseases such as Alzheimer's disease. Furthermore, the research will advance our understanding of the short- and long-term consequences of inflammation on the development and function of the BBB over the lifespan.

    B. Collaborative studies of maternal vs placental influences on fetal brain development:
    Our technological development of the ex vivo perfusion of the mouse placenta has led to numerous collaborative projects aiming at directly assessing the contributions of various maternally vs placentally-derived molecules to fetal brain development. For instance, this technology was applied in a collaborative project with Dr Karsenty (Columbia University) to demonstrate the maternal-fetal transfer of an important neurogenic molecule, osteocalcin, which is synthesized by maternal bone (b). It was also used in a collaboration with Dr Schwarcz (University of Maryland) to investigate the developmental sources of kynurenine and its metabolites (a branch of tryptophan metabolism, also involved in immune regulation of placental function) (c). It was also used in a collaboration with Dr Bale (University of Colorado) to study the effects of stress on maternally and placentally-derived steroid hormones reaching the developing fetus.

    a. Zhao, Q., Dai, W., Chen, H. Y., Jacobs, R. E., Zlokovic, B. V., Lund, B. T., Montagne, A., and Bonnin, A. (2022). Prenatal disruption of blood-brain barrier formation via cyclooxygenase activation leads to lifelong brain inflammation. Proc Natl Acad Sci U S A 119, e2113310119.

    b. Oury F, Khrimian L, Gardin A, Chamouni A, Goeden N, Huang Y, Srinivas P, Gao X, Suyama S, Mann JJ, Horvath T, Bonnin A, Karsenty G. (2013) Maternal and offspring-derived osteocalcin influences brain development and functions. Cell 155(1), 228-41. PMCID: PMC3864001

    c. Goeden N, Notarangelo FM, Pocivavsek A, Beggiato S, Bonnin A, Schwarcz R (2017) Prenatal Dynamics of Kynurenine Pathway Metabolism in Mice: Focus on Kynurenic Acid. Dev Neurosci, 39:519–528.

    Collapse Research 
    Collapse Research Activities and Funding
    Prenatal inflammation disrupts blood-brain barrier development and long-term function.
    NIH R01NS126981Jan 1, 2023 - Jan 1, 2027
    Role: Principal Investigator
    Prenatal disruption of blood-placenta/brain barrier formation programs AD risk later in life.
    BrightFocus Foundation A2019279SJul 1, 2019 - Jul 1, 2022
    Role: PI
    Prenatal stress and antidepressants effects on offspring brain development
    NIH R01MH106806Jun 1, 2016 - May 31, 2021
    Role: Principal Investigator
    An ex-vivo placental perfusion system to study materno-fetal biology
    NIH R21HD065287Sep 30, 2009 - Aug 31, 2012
    Role: Principal Investigator

    Collapse Bibliographic 
    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help. to make corrections and additions.
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    Altmetrics Details PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. SARS-CoV-2 induces blood-brain barrier and choroid plexus barrier impairments and vascular inflammation in mice. J Med Virol. 2024 May; 96(5):e29671. Qiao H, Deng X, Qiu L, Qu Y, Chiu Y, Chen F, Xia S, Muenzel C, Ge T, Zhang Z, Song P, Bonnin A, Zhao Z, Yuan W. PMID: 38747003.
      View in: PubMed   Mentions: 1     Fields:    Translation:HumansAnimalsCells
    2. Editorial: Advances and perspectives in neuroplacentology. Front Endocrinol (Lausanne). 2023; 14:1206072. Vacher CM, Bonnin A, Mir IN, Penn AA. PMID: 37274324; PMCID: PMC10236794.
      View in: PubMed   Mentions: 2     Fields:    Translation:Humans
    3. 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. Mader S, Brimberg L, Vo A, Strohl JJ, Crawford JM, Bonnin A, Carrión J, Campbell D, Huerta TS, La Bella A, Berlin R, Dewey SL, Hellman M, Eidelberg D, Dujmovic I, Drulovic J, Bennett JL, Volpe BT, Huerta PT, Diamond B. PMID: 35442708; PMCID: PMC9973562.
      View in: PubMed   Mentions: 7     Fields:    Translation:HumansAnimals
    4. 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. Zhao Q, Dai W, Chen HY, Jacobs RE, Zlokovic BV, Lund BT, Montagne A, Bonnin A. PMID: 35377817; PMCID: PMC9169666.
      View in: PubMed   Mentions: 9     Fields:    Translation:AnimalsCells
    5. 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. Karahoda R, Horackova H, Kastner P, Matthios A, Cerveny L, Kucera R, Kacerovsky M, Duintjer Tebbens J, Bonnin A, Abad C, Staud F. PMID: 32311818; PMCID: PMC8345021.
      View in: PubMed   Mentions: 22     Fields:    Translation:HumansAnimals
    6. Correction to "In Utero Exposure to Citalopram Mitigates Maternal Stress Effects on Fetal Brain Development". ACS Chem Neurosci. 2020 Feb 05; 11(3):484. Velasquez JC, Zhao Q, Chan Y, Galindo LCM, Simasotchi C, Wu D, Hou Z, Herod SM, Oberlander TF, Gil S, Fournier T, Burd I, Andrews AM, Bonnin A. PMID: 31912736.
      View in: PubMed   Mentions:    Fields:    
    7. In Utero Exposure to Citalopram Mitigates Maternal Stress Effects on Fetal Brain Development. ACS Chem Neurosci. 2019 07 17; 10(7):3307-3317. Velasquez JC, Zhao Q, Chan Y, Galindo LCM, Simasotchi C, Wu D, Hou Z, Herod SM, Oberlander TF, Gil S, Fournier T, Burd I, Andrews AM, Bonnin A. PMID: 31184110; PMCID: PMC6733519.
      View in: PubMed   Mentions: 11     Fields:    Translation:AnimalsCellsPHPublic Health
    8. 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. da L D Barros M, Manhães-de-Castro R, Alves DT, Quevedo OG, Toscano AE, Bonnin A, Galindo L. PMID: 29890156.
      View in: PubMed   Mentions: 3     Fields:    Translation:AnimalsCells
    9. Prenatal Dynamics of Kynurenine Pathway Metabolism in Mice: Focus on Kynurenic Acid. Dev Neurosci. 2017; 39(6):519-528. Goeden N, Notarangelo FM, Pocivavsek A, Beggiato S, Bonnin A, Schwarcz R. PMID: 29080891; PMCID: PMC6338215.
      View in: PubMed   Mentions: 24     Fields:    Translation:Animals
    10. Asian Zika virus strains target CD14+ blood monocytes and induce M2-skewed immunosuppression during pregnancy. Nat Microbiol. 2017 Nov; 2(11):1558-1570. Foo SS, Chen W, Chan Y, Bowman JW, Chang LC, Choi Y, Yoo JS, Ge J, Cheng G, Bonnin A, Nielsen-Saines K, Brasil P, Jung JU. PMID: 28827581; PMCID: PMC5678934.
      View in: PubMed   Mentions: 79     Fields:    Translation:HumansCells
    11. A Placenta-Specific Genetic Manipulation Reprograms Offspring Brain Development and Function. Biol Psychiatry. 2017 07 15; 82(2):81-82. Bonnin A. PMID: 28645358; PMCID: PMC5831337.
      View in: PubMed   Mentions:    Fields:    Translation:Humans
    12. 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. King JR, Velasquez JC, Torii M, Bonnin A. PMID: 28076682; PMCID: PMC5453513.
      View in: PubMed   Mentions: 4     Fields:    Translation:AnimalsCellsPHPublic Health
    13. Impact of Maternal Serotonin Transporter Genotype on Placental Serotonin, Fetal Forebrain Serotonin, and Neurodevelopment. Neuropsychopharmacology. 2017 01; 42(2):427-436. 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. PMID: 27550733; PMCID: PMC5399236.
      View in: PubMed   Mentions: 32     Fields:    Translation:Animals
    14. Maternal Inflammation Disrupts Fetal Neurodevelopment via Increased Placental Output of Serotonin to the Fetal Brain. J Neurosci. 2016 06 01; 36(22):6041-9. Goeden N, Velasquez J, Arnold KA, Chan Y, Lund BT, Anderson GM, Bonnin A. PMID: 27251625; PMCID: PMC4887568.
      View in: PubMed   Mentions: 110     Fields:    Translation:Animals
    15. Maternal Pharmacokinetics and Fetal Disposition of (±)-Citalopram during Mouse Pregnancy. ACS Chem Neurosci. 2016 Mar 16; 7(3):327-38. Velasquez JC, Goeden N, Herod SM, Bonnin A. PMID: 26765210; PMCID: PMC5384759.
      View in: PubMed   Mentions: 8     Fields:    Translation:Animals
    16. Maternal and offspring pools of osteocalcin influence brain development and functions. Cell. 2013 Sep 26; 155(1):228-41. 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. PMID: 24074871; PMCID: PMC3864001.
      View in: PubMed   Mentions: 167     Fields:    Translation:AnimalsCells
    17. Placental serotonin: implications for the developmental effects of SSRIs and maternal depression. Front Cell Neurosci. 2013; 7:47. Velasquez JC, Goeden N, Bonnin A. PMID: 23630464; PMCID: PMC3632750.
      View in: PubMed   Mentions: 44  
    18. 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. Goeden N, Bonnin A. PMID: 23237830; PMCID: PMC5360402.
      View in: PubMed   Mentions: 21     Fields:    Translation:Animals
    19. Insights into the complex influence of 5-HT signaling on thalamocortical axonal system development. Eur J Neurosci. 2012 May; 35(10):1563-72. van Kleef ES, Gaspar P, Bonnin A. PMID: 22607002; PMCID: PMC3359868.
      View in: PubMed   Mentions: 32  Translation:HumansAnimalsCells
    20. The SSRI citalopram affects fetal thalamic axon responsiveness to netrin-1 in vitro independently of SERT antagonism. Neuropsychopharmacology. 2012 Jul; 37(8):1879-84. Bonnin A, Zhang L, Blakely RD, Levitt P. PMID: 22414815; PMCID: PMC3376320.
      View in: PubMed   Mentions: 13     Fields:    Translation:AnimalsCells
    21. Placental source for 5-HT that tunes fetal brain development. Neuropsychopharmacology. 2012 Jan; 37(1):299-300. Bonnin A, Levitt P. PMID: 22157865; PMCID: PMC3238076.
      View in: PubMed   Mentions: 26     Fields:    Translation:HumansAnimals
    22. Fetal, maternal, and placental sources of serotonin and new implications for developmental programming of the brain. Neuroscience. 2011 Dec 01; 197:1-7. Bonnin A, Levitt P. PMID: 22001683; PMCID: PMC3225275.
      View in: PubMed   Mentions: 134     Fields:    Translation:HumansAnimals
    23. A transient placental source of serotonin for the fetal forebrain. Nature. 2011 Apr 21; 472(7343):347-50. Bonnin A, Goeden N, Chen K, Wilson ML, King J, Shih JC, Blakely RD, Deneris ES, Levitt P. PMID: 21512572; PMCID: PMC3084180.
      View in: PubMed   Mentions: 251     Fields:    Translation:HumansAnimals
    24. Serotonin modulates the response of embryonic thalamocortical axons to netrin-1. Nat Neurosci. 2007 May; 10(5):588-97. Bonnin A, Torii M, Wang L, Rakic P, Levitt P. PMID: 17450135.
      View in: PubMed   Mentions: 122     Fields:    Translation:HumansAnimalsCells
    25. 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. Eagleson KL, Bonnin A, Levitt P. PMID: 16025458.
      View in: PubMed   Mentions: 17     Fields:    Translation:AnimalsCells
    26. Molecular signals regulating proliferation of stem and progenitor cells in mouse olfactory epithelium. Dev Neurosci. 2004 Mar-Aug; 26(2-4):166-80. Kawauchi S, Beites CL, Crocker CE, Wu HH, Bonnin A, Murray R, Calof AL. PMID: 15711058.
      View in: PubMed   Mentions: 53     Fields:    Translation:AnimalsCells
    27. Progenitor cells of the olfactory receptor neuron lineage. Microsc Res Tech. 2002 Aug 01; 58(3):176-88. Calof AL, Bonnin A, Crocker C, Kawauchi S, Murray RC, Shou J, Wu HH. PMID: 12203696.
      View in: PubMed   Mentions: 50     Fields:    Translation:AnimalsCells
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