| Title: |
Restricted fetal blood brain barrier permeability in a preclinical model of autism induced by Group B Streptococcus maternal immune activation |
| Authors: |
Digonnet, Margaux; Chevin, Mathilde; Alfaidy, Nadia; Raia-Barjat, Tiphaine; Giraud, Antoine; Sébire, Guillaume |
| Source: |
Journal of Developmental Origins of Health and Disease ; volume 16 ; ISSN 2040-1744 2040-1752 |
| Publisher Information: |
Cambridge University Press (CUP) |
| Publication Year: |
2025 |
| Description: |
Clinical and preclinical data about perinatal inflammation show its implication in brain injuries leading to autism spectrum disorder (ASD). For instance, Group B Streptococcus (GBS) chorioamnionitis generates autistic manifestations in the progeny. However, the precise way(s) how chorioamnionitis exerts its noxious effect on the central nervous system remains to be define. The pathogen-induced inflammatory response effects on the permeability of the blood brain barrier (BBB) have been documented in the mature brain. No study deals with the effect of GBS-induced chorioamnionitis, on the fetal BBB, even though it is one of the most common infection affecting the fetal environment. Given that dysfunctions of several key cells and molecules from the BBB seem to be involved in the pathogenesis of ASD from genetic and/or environmental origins, we hypothesized that pathogen-induced chorioamnionitis affects structurally and functionally the BBB. We used a well-established preclinical model of GBS chorioamnionitis leading to ASD phenotype in male offspring. We document a significant decrease of albumin permeability of the BBB in the white and gray matters of fetuses exposed versus unexposed to GBS chorioamnionitis. In line with this result, a significant increase in the expression of claudin-5 – component of tight junctions of the BBB – is detected in endothelial cells from BBB exposed to chorioamnionitis. Altogether, our results show that beyond genetic determinants, environmental factors such as bacterial infections affect the integrity of the BBB and might be involved in the fetal programming of ASD. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1017/s2040174425100147 |
| Availability: |
https://doi.org/10.1017/s2040174425100147; https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S2040174425100147 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.7B6855BC |
| Database: |
BASE |