Genes connected to the two disorders may only be active for a brief window of time.
The study, while in mice, could provide clues about how the developmental disorders develop. Focusing on a region of the brain known as the subplate, where the first nerve cells develop, researchers at the University of Oxford, King’s College London and Imperial College London found that genes linked to autism and schizophrenia were only active in these regions during early stages of brain development.
Neurons in the subplate region form the foundation for the network of neural connections that eventually crisscross the brain. Studying the way that nerves develop and join this network can reveal where the growth can go wrong and trigger diseases such as autism or schizophrenia.
“Building the brain is like a house of cards. The early connections provide the foundation of the adult structure, and disruption of these may be the source of many developmental flaws. Subplate neurons provide a transient scaffold for the developing cerebral cortex and they assist in the development of the extra connectivity,” says study author Zoltan Molnar of the University of Oxford. “If the scaffold is damaged, then the building shall not be fully functional.”
The researchers mapped and detailed the gene activity in the mouse brains throughout their development from 15-day-old embryos into adulthood. The work confirmed that autism and schizophrenia are developmental disorders that may be established early in life, just at the time when the brain is forming its first connections. The genes connected to both diseases were only expressed in the subplate neurons, and not afterward, suggesting that once their work was done, the disease process had begun.
“It has been suspected for a long time that if the development of the cortex is disrupted by genetic abnormalities or environmental stress, such as prematurity, this would have long-lasting adverse effects on brain development and could lead to problems like ADHD or autism … [This study] focuses attention even more firmly on early brain development as a cause of these distressing neuropsychological problems,” said David Edwards, director of the Centre for the Developing Brain at King’s College London, in a statement.
Does that mean that the genetic changes can be identified and modified in utero to avoid the diseases? Although that’s not clear, says lead study author Anna Hoerder-Suabedissen of the University of Oxford, “The main implication is, for other researchers, that transient structures of the brain are important to our understanding of the healthy and diseased mature brain. We would hope to validate some of the newly identified subplate specific molecules for use on human postmortem tissue, thereby opening new avenues for understanding the normal and abnormal development of human brains.”
The subplate region is very small in the brains of mice and is much more evolved in human brains. So the researchers are hopeful that their findings offer hope that the genetic links found in the region during early development would be even more distinct and identifiable in human brains.
“I believe that the study … may be a first step toward more findings of such links in the future and opens a possibility to examine more directly the effect of genetic manipulation or exposure to various environmental factors in animal models,” said Pasko Rakic, a professor of neurobiology and neurology at Yale University, one of the first researchers to discover subplate neurons in the 1970s.
The research is published Proceedings of the National Academy of Sciences.