In the brains of people with autism, microglial cells (a type of support cell) appear to be constantly activated, with genes for inflammation responses perpetually turned on, according to a new collaborative study by researchers at Johns Hopkins University School of Medicine and the University of Alabama at Birmingham.
“This type of inflammation is not well understood, but it highlights the lack of current understanding about how innate immunity controls neural circuits,” said Andrew West, Ph.D., an associate professor of neurology at the University of Alabama.
Given the known genetic contributors to autism, inflammation is unlikely to be its root cause, said Dan Arking, Ph.D., an associate professor in the McKusick-Nathans Institute for Genetic Medicine at Johns Hopkins. Rather, said Arking, “This is a downstream consequence of upstream gene mutation.”
While many different combinations of genetic traits can cause autism, brains affected by autism share a pattern of overactive immune responses. The study involved data from 72 autopsied brains of people with and without autism.
“There are many different ways of getting autism, but we found that they all have the same downstream effect,” says Arking. “What we don’t know is whether this immune response is making things better in the short term and worse in the long term.”
The causes of autism are still unclear and are a frequent research topic for geneticists and neuroscientists. But Arking had noticed that for autism, studies of whether and how many genes were being used — known as gene expression — always involved too little data to draw many useful conclusions.
This is because, unlike a genetic test, which can be performed using nearly any cells in the body, gene expression testing has to be done on the specific tissue of interest — in this case, brains that could only be obtained through autopsies.
For the study, the researchers analyzed gene expression in samples from two different tissue banks, comparing gene expression in people with autism to that in controls without the disorder. This amounted to 104 brain samples from 72 individuals — the largest data set so far for a study of gene expression in autism.
“The next step,” says Arking, “will be to find out whether treating the inflammation could lessen the symptoms of autism.”
The study was published online in the journal Nature Communications.
Source: Johns Hopkins Medicine