Summary: New research from Nagoya University indicates that maternal inflammation during pregnancy can interfere with infant brain development by reducing a specialized population of immune cells in the brain — CD11c-positive microglia. These cells produce IGF-1, a growth factor essential for forming myelin, the insulating sheath that enables fast, efficient nerve signal transmission. The study links lower IGF-1 and fewer CD11c-positive microglia to delayed myelination detected by MRI in preterm infants exposed to prenatal inflammation, highlighting a possible therapeutic target to protect neurodevelopment.
Researchers examined both an animal model and human samples to investigate how maternal immune activation affects early brain maturation. In mice exposed to prenatal inflammation, induction and proliferation of CD11c-positive microglia were suppressed during the early postnatal period. In parallel, cord blood from preterm infants with chorioamnionitis—an inflammatory condition of the fetal membranes—showed lower IGF-1 and higher proinflammatory cytokines. MRI at term-equivalent age revealed a higher rate of delayed myelination among infants with exposure to maternal inflammation.
Key Facts:
- Cell type affected: CD11c-positive microglia are reduced following prenatal inflammation.
- Biomarker change: IGF-1 levels are lower in cord blood of exposed preterm infants.
- Developmental outcome: Reduced microglial IGF-1 production correlates with delayed myelination on MRI.
- Clinical implication: Preserving or restoring CD11c-positive microglial function could be a strategy to reduce long-term neurodevelopmental risk.
Published in Communications Biology, the study was led by Kazuya Fuma and Tomomi Kotani at Nagoya University Graduate School of Medicine. It addresses how maternal inflammation—triggered by infection, autoimmune activity, or environmental stressors—may set the stage for altered neurodevelopment through immune-mediated disruption of early white matter formation.
Microglia are the brain’s resident immune cells and perform diverse roles during development beyond host defense. A transient surge of CD11c-positive microglia normally occurs in the early postnatal period and supports myelination by supplying IGF-1. In the mouse model of maternal immune activation used in this study, the population of these CD11c-positive microglia was significantly reduced on postnatal day 3, and myelination-related proteins were decreased by postnatal day 8. These temporal findings suggest that a brief window of impaired microglial support can have measurable effects on myelin formation.
To connect the mouse data with human outcomes, the team analyzed cord-serum samples from preterm infants diagnosed with histological chorioamnionitis (HCA). Compared with infants without HCA, those exposed to inflammation had elevated inflammatory cytokines such as IL-6 and IL-17A, along with lower IGF-1 levels. Follow-up MRI studies at term-equivalent age showed a greater frequency of delayed myelination in the inflammation-exposed group, consistent with the mouse model findings.
Fuma notes, “Inflammation during pregnancy suppressed the normal increase in CD11c microglia observed in early development. Because these microglia are an important source of IGF-1, their reduction likely contributes to impaired myelination and may underlie some neurodevelopmental delays.”
The research emphasizes a potentially actionable pathway: protecting or restoring CD11c-positive microglia or augmenting IGF-1 signaling during the vulnerable perinatal period might reduce the risk of delayed white matter development and subsequent cognitive or behavioral impairments. The authors stress the need for further studies to confirm whether similar microglial changes occur in human infants and to evaluate safe, targeted interventions.
About this maternal inflammation and neurodevelopment research news
Author: Matthew Coslett
Source: Nagoya University
Contact: Matthew Coslett, Nagoya University
Image credit: Neuroscience News
Original Research: Open access. Title: “Prenatal Inflammation Impairs Early CD11c-Positive Microglia Induction and Delays Myelination in Neurodevelopmental Disorders” by Kazuya Fuma et al., Communications Biology.
Abstract (concise):
Histological chorioamnionitis (HCA), a form of maternal immune activation, is associated with increased risk of neurodevelopmental disorders in offspring. This study examined the role of CD11c-positive microglia—cells that contribute to myelination through IGF-1 production—in a mouse model of maternal inflammation and in human preterm infants exposed to HCA. In mice, the CD11c-positive microglial population was significantly lower early postnatally in the inflammation-exposed group, with a subsequent decrease in myelination-related proteins. In human cord blood, infants with HCA exhibited higher inflammatory cytokines and lower IGF-1, and a higher incidence of delayed myelination on MRI at term-equivalent age. Comparative analysis indicates a transient induction of CD11c-positive microglia during early development in both species, and a lack of this high microglial population has been noted in children with neurodevelopmental disorders. These findings point to impaired induction of CD11c-positive microglia as a mechanism linking prenatal inflammation to delayed myelination and offer a rationale for developing interventions to improve outcomes in affected infants.