Neonatal inflammation impairs developmentally-associated microglia and promotes a highly reactive microglial subset
Microglia and border-associated macrophages play critical roles in both immunity and neurodevelopment. The disruption of microglial development trajectories by neonatal inflammation is an important issue in research on neurodevelopmental disorders (NDDs), as models have suggested a strong association between inflammation and cognitive deficits. Here, we explored by single-cell RNA sequencing and flow cytometry the impact of neonatal inflammation in a mouse NDD model on brain myeloid cell subsets. A specific subset of microglia expressing the complement receptor C5ar1 has been identified, in which inflammatory pathways are most strongly activated. Based on transcriptional similarity, this subset appears to originate from the most mature and "homeostatic" microglia at this stage of development and demonstrated hypersensitivity to inflammation. Besides that, Spp1-microglia supporting oligodendrocyte differentiation, primitive and proliferative microglia were reduced by inflammation. These findings suggest major changes in microglial subsets developmental trajectories and reactivity contributing to NDDs induced by neonatal inflammation.
Authors
- Juliette Van Steenwinckel (ORCID: https://orcid.org/0000-0003-3463-4856)
- Andrew D. Griffiths (ORCID: https://orcid.org/0000-0002-0808-3539)
- Sophie Foulon
- Clémence Réda (ORCID: https://orcid.org/0000-0003-3238-0258)
- Amazigh Mokhtari (ORCID: https://orcid.org/0000-0002-6438-8978)
- Pierre Gressèns
- Cindy Bokobza (ORCID: https://orcid.org/0000-0003-0992-4317)
- Andrée Delahaye‐Duriez (ORCID: https://orcid.org/0000-0003-4324-7372)
- Philippe Nghe (ORCID: https://orcid.org/0000-0003-3690-4610)
- Valérie Faivre (ORCID: https://orcid.org/0000-0001-6392-2297)
- Adrien Dufour (ORCID: https://orcid.org/0000-0001-5790-3401)
- Jennifer Hua (ORCID: https://orcid.org/0000-0003-2014-918X)
- Ariane Heydari Olya
Institutions
- Inserm (FR)
- Délégation Paris 7 (FR)
- Université Paris Cité (FR)
- AgroParisTech (FR)
- Université Paris-Saclay (FR)
- Microbiologie de l’alimentation au service de la santé (FR)
- Sorbonne Université (FR)
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- Université Sorbonne Paris Nord (FR)
- Sorbonne Paris Cité (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- NeuroDiderot (FR)
- ESPCI Paris (FR)
Publication Details
- Journal
- Brain Behavior and Immunity
- Published
- 2024-09-23
- DOI
- https://doi.org/10.1016/j.bbi.2024.09.019
- Citations
- 9
- Primary Topic
- Neuroinflammation and Neurodegeneration Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 2.23