University of Maryland researchers discover for the first time how inflammation can affect brain development and contribute to the risk of autism spectrum disorders
New research by a team of researchers from the University of Maryland UMSOM School of Medicine has shown, for the first time, how inflammation in early childhood can affect brain development and contribute to the risk of autism spectrum disorders (ASD) and schizophrenia.
The results show that inflammation can lead to genetic changes in areas of the brain associated with higher cognitive functions and may play a role in a variety of neurological and psychiatric disorders, according to what was published by the “New Atlas” website, citing the journal “Science Translational Medicine.”
Natural immune system
The human body’s immune system crucially protects against a variety of microbial attackers, and inflammation is the front-line response of the immune system when the human body faces injury or infection.
However, the body’s inflammatory response can occasionally behave like a crude tool, resulting in unintended harm while attempting to locate pathogens. In instances of chronic autoimmune disease, this can inadvertently eliminate healthy cells, leading to prolonged illness.
Maternal exposure to infections during pregnancy is recognized to have an impact on fetal neurodevelopment. Numerous observational studies have established a connection between viral and bacterial infections during pregnancy and a heightened risk of autism and schizophrenia in children. However, it has remained unclear whether these inflammatory responses persist in disrupting neurodevelopment during the early years of a child’s life. To delve deeper into this matter…
Epigenetic changes in the cerebellum
In a first-of-its-kind study led by Seth Ament, of the University of Maryland Genomics Institute, and Margaret McCarthy, director of the Neuroscience Discovery Institute, researchers have shown directly how inflammation can affect neurodevelopment.
The researchers obtained post-mortem brain tissue from 17 deceased children. Half of the participants had succumbed to severe infections, while the other half had experienced sudden deaths due to accidents. The study specifically examined the epigenetic modifications occurring in the cerebellum region of the brain.
RNA sequencing
Ament explained that the focus was on the cerebellum “because it is one of the first regions of the brain that begins to develop and one of the last regions to reach maturity, but it is still not studied,” noting that with the use of the somewhat new method represented by DNA sequencing “Single-nucleus RNA can look down to the cellular level to see changes in brains.”
Rare cerebellar cells
The results revealed that two specific types of cerebellar neurons were particularly sensitive to inflammation: Golgi and Purkinje neurons. Although these two cell types are relatively rare, Ament says they play crucial roles in cognition and behavior.
As Purkinje neurons develop, they establish synapses connecting the cerebellum to brain regions associated with cognition and emotional control. Simultaneously, Golgi neurons facilitate communication among cerebellar cells. Ament explains that disrupting these developmental processes can shed light on the role of inflammation in conditions like autism spectrum disorders and schizophrenia.
Stifling cellular maturation
In cells exposed to inflammation, the researchers discovered epigenetic changes that were consistent with the downregulation of developmental gene expression programs. In other words, inflammation appeared to be stifling cellular maturation in these critical regions of the brain.
Maureen Cowan, a scientist at the University of Virginia, whose research focuses on neuroinflammation, finds the new study intriguing. She notes that the tissue samples collected from the inflammatory group encompass patients with various conditions, ranging from meningitis to asthma. However, despite the heterogeneity of this group, there is a consistent cellular effect, indicating that different sources of inflammation result in similar impacts on the brain.
The suffering is complete at the age of 5 years
Professor Ament explains that children begin to experience many of these neurological changes at about 12 months of age, explaining that current data indicate that “the greatest vulnerabilities begin when children reach their first year,” stressing that “the gene expression patterns that have been discovered indicate that… “Many of these developmental processes are complete when children are approximately 5 years old. However, additional samples of infants and older children still need to be studied to fully determine these time courses.”
Genetics and environment
The researchers advise against solely emphasizing inflammation as a single causal factor in the development of disorders like autism spectrum disorder and schizophrenia. They highlight the significant roles that genetics and environment play in neuropsychiatric diseases. Therefore, the occurrence of viral infections in young children should not be considered the sole cause of autism.
