Prenatal Disruption of Blood-placenta/Brain Barrier Formation Programs AD Risk Later In Life
Recent animal model studies suggest a causal link between inflammation during embryonic development and risk of Alzheimer’s disease-like neuropathology later in life. In light of recent research demonstrating that blood-brain barrier breakdown in the adult brain is a core cause of Alzheimer’s disease, we hypothesize that inflammation-mediated disruption of blood-placenta and blood-brain barriers are key factors in the developmental origins of Alzheimer’s disease. This project, which explore understudied mechanisms and factors contributing to Alzheimer’s disease etiology, will provide invaluable insights into the developmental origins of this devastating disease.
Using cutting-edge live imaging techniques in a mouse model, the goal of this project is to uncover the cellular and molecular mechanisms by which inflammation disrupts blood-brain barrier formation and function during and after pregnancy, leading to Alzheimer’s disease-like phenotypes in the adult offspring.
Our rigorous approach monitors prenatal inflammation effects on blood-barriers formation and function longitudinally, from the fetal to the postnatal and adult stages of offspring life. These techniques will be combined with behavioral measures and post-mortem histochemical quantification, throughout the lifespan, of specific molecular markers of blood-barriers establishment and function and of Alzheimer’s disease-related neuropathology. Furthermore, the influence of “gene by environment interactions” will be investigated by testing the impact of prenatal inflammation on the severity of phenotypes in well-characterized transgenic mouse models of Alzheimer’s disease.
This project explores vastly understudied mechanisms and factors contributing to Alzheimer’s disease etiology and will provide invaluable insights into the developmental origins of this devastating disease. The potential discovery of new cellular and molecular pathways, where genes and environment interact and either trigger or increase AD risks, could uncover new therapeutics targets by which disease progression could be slowed down or even prevented all together. Given the very basic science nature of our proposal, potential therapeutic benefits may not be immediate; however, we hope the discoveries brought by this project will lead to identifying new risks for AD etiology, and preventative early interventions in future human generations.
About the Researcher
Dr Alexandre Bonnin is Associate Professor of Physiology and Neuroscience in the Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California. His research explores maternal-fetal interactions contribution to shaping fetal brain development during pregnancy. In particular, he focuses on identifying new molecular pathways by which prenatal events influence the onset of mental diseases in the adult offspring. These efforts will provide new directions to study the developmental origin of mental health-related disorders in humans.
Dr Bonnin received his PhD in neuroscience from the University of Paris and the Pasteur Institute in Paris, France. He completed postdoctoral fellowships in developmental neurobiology at the University of California Irvine and later at Vanderbilt University (USA) before joining the University of Southern California as an assistant professor in 2011. Dr Bonnin was awarded grants from the NIMH, US Department of Defense and several Young Investigator Awards by the Brain & Behavior Research Foundation and was the recipient of a 2011 Daniel X. Freedman Award for outstanding basic research achievement.
My research career has been focused on understanding the molecular and cellular mechanisms of brain development. In particular, I have been investigating how a neurotransmitter, serotonin, can also act as a trophic factor and affect various aspects of neurodevelopment such as axonal guidance and cerebral cortex formation. The research project funded by BrightFocus is a completely new directions that will uncover important clues for understanding the developmental origins of neurodegenerative disorders such as Alzheimer’s disease. The very generous support from BrightFocus Foundation and its donors will be critical to identifying new risks for Alzheimer’s disease etiology, and ultimately help develop preventative early interventions in future human generations.
First published on: June 26, 2019
Last modified on: July 2, 2019