Research from the University of California Davis has contributed to mounting evidence linking a risk of autism with a mother’s prenatal health and immune system activity. The study is the first to connect immune responses in pregnant mothers and changes in the neural development in their offspring. The findings may eventually lead to diagnostic tests for these types of disorders.
The research team used mice and rats to conduct the study. Some of the pregnant animals were exposed to a viral infection that activated the immune system, but others were not exposed to the contagion. Once the rodents gave birth, the researchers compared the offspring of both groups. They found that the pups of the animals that had been exposed to the viral infection had higher levels of MHCI (major histocompatilibty complex I) immune molecules—a set of cells that mediate white blood cells—in the brain.
This study builds upon previous works that suggest a possible cause of autism spectrum disorders and schizophrenia could be a disruption to the normal development of neural pathways, particularly in the cerebral cortex. The researchers discovered that high MHCI levels muted the newborn mice’s brains’ ability to form synapses and make appropriate neural connections.
The study also resulted in the discovery of a biological signaling pathway that had never before been identified. The pathway is created through a combination of MHCI, calcineurin (an activator of the immune system’s T-cells), and Mef2 (a transcription protein important for embryonic development). The research team not only identified the pathway, but also found that it was more active in the offspring of the mice who had not been exposed to the viral infection. This finding suggests that there may be a way to develop tests and, eventually, treatments, for neurodevelopmental disorders.
“This is the first evidence that neurons in the developing brain of newborn offspring are altered by maternal immune activation. Until now, very little has been known about how maternal immune activation leads to autism spectrum disorder and schizophrenia-like pathophysiology and behaviors in the offspring. This finding provides a potential mechanism linking maternal immune activation to disease-linked behaviors,” stated Kimberly McAlilister, senior author of the study, professor at the Center for Neuroscience and researcher with the UC Davis MIND Institute.
This research is published in the Journal of Neuroscience.
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