Researchers show that molecule known for fighting infections also crucial for pruning away excess brain connections
Researchers have discovered that a major immune-system molecule – called MHCI, for major histocompatibility complex class 1 – does double duty in the brain by controlling the number of synapses, or brain cell connections.
The study, funded in part by Autism Speaks, appears this week in The Journal of Neuroscience.
The finding raises the possibility that changes in MHCI’s normal activity could play a previously unrecognized role in the development of autism, says co-author Lawrence Fourgeaud. Dr. Fourgeaud’s research was made possible by an Autism Speaks postdoctoral fellowship. Senior author Lisa Boulanger served as Dr. Fourgeaud’s fellowship mentor at the University of California San Diego and is now at the Princeton Neuroscience Institute.
“We’ve long known that immune system dysfunction is a key feature of autism in some individuals,” comments Dan Smith, Autism Speaks senior director for discovery neuroscience. “The same can be said for the growth and fine-tuning of synaptic connections. This study takes us to a new place by demonstrating one way these things may be linked. We’re proud to see such progress come from one of our postdoctoral fellows.”
MHCI proteins are known for their role in the immune system where they present protein fragments from disease-causing microbes and cancerous cells to T cells. (T cells are akin to the “generals” of the immune system, directing the body's response to infection or cancer.)
In the brain, however, the researchers found that MHCI molecules play a major role in limiting the number of connections between brain cells. They do so by inhibiting insulin receptors, which promote synapse formation. Tight control over the number and location of synapses is essential for healthy brain development and function. Moreover, previous research has associated autism with an over-abundance of synapses in certain brain regions.
This is intriguing since inflammation during pregnancy alters MHCI levels in the fetal brain and may increase the risk of autism in genetically predisposed individuals, Dr. Boulanger says.
“While these results do not directly link MHC1 to autism-related brain alterations, they have important, broader-reaching implications for our understanding of how the immune system and the brain interact,” Dr. Smith adds. “This is certainly worthy of follow-up research.”
For more, see:
“Study on Autism and Synapses Sheds New Light on Brain Structure”
“Paul Wang Discusses Breakthrough Synapse Study on Al Jazeera America”
"Immune Proteins Moonlight to Regulate Brain-cell Connections”