Venue: Centre Broca
Pauline Montguillon
NutriNeuro
Title
From inflammation to nutrition, impact of the environment in neurodevelopmental disorders
Abstract
Various environmental influences are known to increase the risk of neurodevelopmental disorders (NDD), such as autism spectrum disorder (ASD), including perinatal inflammation and dietary factors. Perinatal inflammation induces long-lasting activation and modification of microglia, leading to alteration of the developing brain programming. Relevant models are the Maternal Immune Activation (MIA) and the postnatal Interleukin-1β (IL-1β) models, involving injections of inflammatory agents during either gestation or the first days after birth. Previous studies established that offspring from MIA and IL-1β models exhibit cellular NDD phenotypes, initially observed primarily in males. In addition, a microglia renewal approach using a CSF1R inhibitor (PLX5622) in the MIA model successfully restored social behaviour abilities at adulthood in males. Here, we aim to explore the potential shared benefits of microglia renewal strategy on NDD phenotype at adulthood using two rodent models of NDD, MIA and IL-1β models, in both sexes. Our results indicate that the microglia renewal partially restores deficits induced by the models on social and cognitive dimensions, including a consistent restoration of sociability deficits in males and females from both models at adulthood. Given the invasive nature of microglia renewal, we further investigated the mechanisms underlying its beneficial effects. First, we managed to identify the interferon-γ pathway as a potential master regulator of microglia response to cellular renewal in MIA condition, giving us a target to causally link the beneficial effect of our PLX approach onto MIA-induced behavioural deficits at adulthood. Then, we demonstrated that, in our experimental condition, the effects of PLX may rely on different pathways depending on the sex: while interferon-γ receptor is necessary to observe the rescue of social deficits in females, a knockout of this receptor does not alter the effects of microglia renewal in males. In a second axis, we investigated a specific inflammatory risk factor for NDDs: food consumption during development. Regarding dietary risk factors, we focused on ultra-processed food, and more specifically what distinguishes them from other alimentary products: food additives. We studied the effect of titanium dioxide (TiO2 – E171) and silicon dioxide (SiO2 – E551) from gestational period on brain development, alone or in combination at doses relevant to human exposure, to reflect realistic human consumption. We revealed that exposure to TiO2 and SiO2 induces deficits during the developmental period, associated with cognitive alterations later in life at juvenile and adult periods, recapitulating key NDD features. These behavioural alterations are associated with an altered inflammatory profile in several brain structures playing a key role in NDD, such as the hippocampus, specific to toxicant. Overall, my PhD project aims to understand how environmental factors during development can induce NDD phenotype and provides novel knowledge on innovative interventional strategies notably targeting microglia to restore optimal brain functions at adulthood for individuals with NDDs.
Key words : neurodevelopmental disorders / environment / microglia / food additives / animal models
Publications
Delpech JC, Yeh H, Kalavai SV, You Y, Ruan Z, Touch N, Hersh S, Monguillon P, Johnson WE, Rau A, Madore C, Ikezu T & Ikezu S
Sex specific correction of maternal inflammation-induced behavioral abnormalities by the inhibition of colony-stimulating factor 1 receptor.
Brain Behav Immun. 2026 Jan;131:106163. doi: 10.1016/j.bbi.2025.106163. Epub 2025 Nov 2. PMID: 41187794.
Preprint publications
Monguillon P, Bondad S, Lamas B, Houdeau E, Delpech JC, Layé S & Madore-Delpech C –
Combined and isolated lifelong exposure to TiO2 and SiO2 disrupts neurodevelopment and behavior in a sex-specific manner
Monguillon P*, Naffaa V*, Dupont-Viratelle J, Gibert A, Gressens P, Layé S, Van Steenwinckel J# & Delpech JC#
Microglia renewal strategy alleviates behavioral and biological alterations induced by neonatal inflammation in a sex-dependent manner.
Monguillon P, Yeh H, Dupont-Viratelle J, Crespo F, Ikezu T, Kalavai S, Van Steenwinckel J, Gressens P, Madore-Delpech C, Layé S, Ikezu S# & Delpech JC#
Interferon-g signalling mediates the benficial effects of microglial renewal in maternal inflammation-induced socibility impairment at adulthood in a sex-dependent manner
Monguillon P, Naffa V, Marniquet I, Crespo F, Séré A, Madore-Delpech C, Layé S, Gressens P, Delpech JC# & Van Steenwinckel J# –
Evaluation of a novel FCRLS-cre mouse strain at adulthood shows specific but limited microglial recombination efficacy and no behavioral alterations.
Jury
- Dr. Laetitia Davidovic – Rapportrice
Directrice de recherche, IPMC (Valbonne) - Dr. Véronique Perrier – Examinatrice
Directrice de recherche, INM (Montpellier) - Dr. Andreas Frick – Examinateur
Directeur de recherche, Neurocentre Magendie (Bordeaux) - Dr. Freddy Jeanneteau – Examinateur
Directeur de recherche, IGF (Montpellier) - Dr. Morgane Thion – Rapportrice
Chargée de recherche, Collège de France (Paris) - Dr. Jean-Christophe Delpech – Directeur de thèse
Chargé de recherche, NutriNeuro (Bordeaux) - Membres invités :
Dr. Julie Le Merrer Directrice de recherche, iBrain (Tours)
Dr. Sophie Layé Directrice de recherche, NutriNeuro (Bordeaux)