Genetic study in mice maps pathway linked to neurodevelopmental defects in offspring

Stress during pregnancy such as gut changes or a trigger of the immune system can impact the brain health of the foetus, potentially paving way for neurodevelopmental abnormalities to develop, according to a new genetic study in mice.

In a paper published in the journal Nature Neuroscience, researchers have mapped how stress events during pregnancy can affect the neuroimmune landscape of the developing foetal brain using spatial transcriptomics — they help reveal which genes of a tissue were active and where.

“Our study establishes a detailed spatial transcriptomic resource of immune gene networks during a critical window of embryonic brain development,” lead researcher Brian Kalish, a physician in the division of newborn medicine at US’ Boston Children’s Hospital, said.

The study mapped the location of gene relevant to the neurodevelopment of the developing brain.

The researchers also discovered notable sex-specific responses in the foetus, such as a vulnerability for a specific immune pathway in the male brain, that could be a potential target for early intervention.

“Unlike previous atlases focused on the adult brain, our dataset captures dynamic immune signalling interactions at a stage when the brain is highly vulnerable,” Kalish said.

Further, the team also proposed a specific pathway in the immune system — known as the ‘CXCL12/CXCR7’ signalling pathway — important for neural stem cells to incorrectly develop as neurons, potentially resulting in structural or functional defects.

“As a neonatologist, this work adds to our understanding early-life environmental factors that may impact neurodevelopmental potential and lends insights for potential interventions,” Kalish said.

The authors “determined how embryonic neuroimmune landscape was altered after maternal immune activation and maternal microbiome depletion.”

“This resource underscores how the maternal environment programs precise regulation of immune molecules in developing brain, highlighting sex-specific vulnerability,” they said.