Stress during pregnancy, including gut alterations or triggers of the immune system, can influence foetal brain health and potentially lead to neurodevelopmental abnormalities, according to a new genetic study conducted in mice. The lead researcher is Brian Kalish, a physician in the division of newborn medicine at Boston Children’s Hospital, US.
Published in the journal Nature Neuroscience, the study mapped how stress events during pregnancy impact the neuroimmune landscape of the developing foetal brain using spatial transcriptomics, a technique that identifies which genes are active in specific regions of tissue. The research established a detailed spatial transcriptomic resource of immune gene networks during a critical period of embryonic brain development, revealing the precise location of genes relevant to neurodevelopment.
The study also uncovered notable sex-specific responses in the foetus, including a particular vulnerability in the male brain linked to a specific immune pathway, which could serve as a target for early intervention. Unlike previous atlases that focused on adult brains, this dataset captures dynamic immune signalling interactions at a stage when the brain is especially susceptible.
Researchers identified the 'CXCL12/CXCR7' signalling pathway in the immune system as crucial for neural stem cells, with disruptions potentially causing them to develop incorrectly as neurons, resulting in structural or functional defects. The study further demonstrated how maternal immune activation and depletion of the maternal microbiome altered the embryonic neuroimmune landscape.
Overall, the findings highlight how the maternal environment precisely regulates immune molecules in the developing brain and underscores sex-specific vulnerabilities that may influence neurodevelopmental outcomes, providing potential avenues for early interventions.
