Preeclampsia and Maternal Dementia: An Exploration of Cerebrovascular Changes and Potential Therapeutic Targets
Preeclampsia (PE) is a pregnancy-specific complication associated with hypertension and placental hypoperfusion, as well as elevated levels of circulating inflammatory factors secreted by the placenta, which leads to an increased risk of adverse neonatal outcomes for both the fetus and the mother, as well as consequences for neurovascular function. However, PE is not limited to pregnancy, and more than 20 years after the event, women remain at increased risk of stroke and cognitive impairment. Clinical MRI studies have shown that these patients exhibit brain lesions. MAB2’s research on a mouse model of PE has demonstrated the direct involvement of inflammatory factors, including prokinetins (PROKs) and their receptors. We have shown in a cellular model of the blood-brain barrier that PROKs alter vascular permeability.
Our recent results demonstrate a direct link between the preeclampsia event and the onset of late-onset brain damage and inflammation. Finally, recent metabolomics and proteomics findings support the hypothesis that genome-wide disruptions in the histone modification profile may be involved in vascular alterations and the development of vascular and/or neurodegenerative dementia.
The objective of the project is to characterize the vascular changes that occur at the onset of PE and their long-term consequences on cognitive function, and to identify potential therapeutic targets for preventive treatment. These objectives will be addressed through MRI studies, behavioral tests, and analysis of epigenetic modifications using a mouse model of preeclampsia.
PREDEV Project Partners
Christel MARQUETTE; BIOSANTE
Delphine PFLIEGER; BGE EDYP
Sabine BRUGIERE; BGE EDYP
Emmanuel BARBIER; GIN IRMaGe
Mireille ALBRIEUX; GIN
Lise MIGUEL, Ph.D. candidate in the PREDEV project
Who is she?
I earned a bachelor’s degree in Cell Biology and Physiology at the University of Limoges, where I was introduced to neuroscience. I then went on to pursue a master’s degree in Neuroscience at the University of Strasbourg.
During my first year of the master’s program, I joined the Life Adversities and Pain team at the Laboratory of Cognitive and Adaptive Neurosciences in Strasbourg for an internship under the supervision of Professor Lelièvre and Edith Tanché. This project focused on the effects of gestational stress in mouse embryos deficient in Vasoactive Intestinal Peptide, with the aim of studying the placental, inflammatory, and behavioral consequences in adulthood. In my second year, I completed an internship at University College London, working with Dr. Sandrine Géranton and Dr. Francesca Di Domenico. My work focused on the effects of radiation therapy and stress on pain perception in mice, by studying the brain and spinal circuits involved in pain modulation.
I am currently pursuing a Ph.D. in neuroscience under the supervision of Christel Marquette at the CEA’s Biosanté laboratory in Grenoble. My research focuses on post-preeclampsia vascular dementias, specifically the role of prokineticins in cerebrovascular alterations and the epigenetic changes associated with preeclampsia.
Preeclampsia is a hypertensive disorder of pregnancy characterized by placental hypoxia, which triggers the release of several inflammatory and angiogenic factors, including prokineticins (PROK1 and PROK2). These proteins, by acting on their receptors (PROKR1 and PROKR2), disrupt the blood-brain barrier (BBB), leading to cerebrovascular damage and inflammatory processes. At the same time, epigenetic changes, particularly at the histone level, may disrupt gene expression and contribute to neurodegenerative processes. In the long term, women who have had preeclampsia are at increased risk for stroke and cognitive impairment.
My thesis aims to characterize, in a preeclampsia mouse model, cerebrovascular alterations using MRI, their long-term consequences on cognitive function (Barnes test), as well as epigenetic changes affecting the hippocampus, the cortex, and the BBB. Finally, the efficacy of a preventive treatment—based on a prokinetin receptor antagonist—will be evaluated to limit cerebrovascular damage and prevent cognitive deficits.
This project addresses a major public health issue: improving care for pregnant women and preventing cognitive complications that may arise several years after pregnancy.
Link to partner laboratories