Cerebroid study hints at how maternal inflammation may influence fetal brain development
Past studies suggest that a mother-to-be's heightened immune responses during pregnancy are linked to a higher risk of conditions affecting their offspring's brain development. While this association is well documented, the processes through which immune responses might alter the developing brain remain unclear.
A recent study from the University of Aberdeen has provided insights into how maternal inflammation may impact fetal brain development. Previous research has shown that heightened immune responses in expectant mothers are linked to an increased risk of brain development issues in their offspring. However, the mechanisms behind this association remain largely unclear.
To address this knowledge gap, the researchers developed cerebroids, which are three-dimensional (3D) pieces of developing human cerebral cortex maintained outside the body, to better understand the effects of maternal immune responses on fetal brain development. Their findings, published in Nature Neuroscience, suggest a potential pathway linking maternal immune activation to fetal brain development differences.
Maternal immune activation during pregnancy has been associated with a higher risk of neurodevelopmental conditions, but the direct effects of inflammation on fetal brain development are not yet fully understood. Dr. Daniel Berg, co-senior author of the study, explained that the cerebroid model was created to overcome limitations in brain organoid research, which often fail to fully replicate the complexity and organization of human brain tissue.
The study utilized human fetal brain tissue from the dorsolateral prefrontal cortex, collected following elective termination of pregnancy. Exposed to IL-17A, an inflammatory signaling protein linked to maternal immune activation, the cerebroids underwent various assessments, including microscopy, cell-labeling approaches, and molecular analyses.
The researchers discovered that IL-17A exposure led to premature folding of the developing human cortex, increased cortical thickness, and accelerated production and maturation of neurons. Blocking the NF-κB signaling pathway, which was identified as a key mechanism, reversed many of the observed changes. While the study does not prove that maternal inflammation directly causes neurodevelopmental conditions, it provides valuable insights into how inflammatory signals might influence early brain development.
Future research could further explore these biological pathways in cerebroids, organoids, and animal models. The researchers aim to gain a deeper understanding of how different cell types in the developing brain respond to inflammatory signals associated with maternal immune activation, including immune cells, developing blood vessels, and neural stem cells.
They also plan to create cerebroid models of other brain regions to investigate whether other areas are similarly affected by immune or inflammatory signals and other environmental factors. Ultimately, the findings could help identify strategies to protect healthy brain development by understanding the pathways that make the developing brain vulnerable to inflammation.
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