A small molecule in the brain called interleukin 34, or IL34, may play a big role in how young brains grow and form the connections that shape how we feel, think, and learn.
In a new study in mice, Duke University researchers discovered IL34 fine tunes the behavior of the brain’s immune cells by telling them when to start and when to stop trimming connections between brain cells.
This microscopic pruning is a normal part of healthy brain development. But when the process goes off track, it may contribute to conditions like autism and Alzheimer’s disease.
Staci D. Bilbo, PhD, professor of psychology and neuroscience at Duke Trinity College of Arts and Sciences and an immunology and neurobiology researcher at Duke School of Medicine, said the findings add to a growing body of research showing the brain doesn’t develop on its own.
“It relies on constant communication with immune cells to guide how it grows and functions,” said Bilbo, senior author of the study published July 2 in Immunity.
For decades, neuroscientists viewed specialized immune cells, known as microglia, mainly as the brain’s defenders against infection or injury. Until recently, scientists didn’t know they played a role in sculpting brain connections. Now they’re starting to understand just how critical and precise the role is.
Timing is Everything
The new findings suggest that shortly after birth, neurons use IL34 as a chemical signal to tell immune cells that it’s time to grow up and start pruning with care.
Synaptic pruning of weak or extra connections between brain cells helps make room for stronger, more efficient circuits that support emotions and decision-making.
When researchers blocked IL34 in young mice, they saw microglia remain immature. Without the signal, microglia continued pruning for too long, and important brain regions like the anterior cingulate cortex which handles social behavior and emotions ended up with missing connections.
But when IL34 was artificially boosted too early, microglia matured faster and engaged in excessive pruning, endangering the brain’s emerging circuits.
“The developmental timing of microglial pruning is so critical because it ensures the appropriate preservation and maintenance of important synaptic connections between neurons,” said Benjamin Devlin, first study author and a Trinity graduate student. “If pruning is too early, or too late, it can have profound consequences for the proper functioning of our brains.”
Mistimed or excessive pruning may play a role in brain disorders, Devlin said. In autism, there may be too many excitatory connections, and not enough inhibitory ones leading to an overactive brain. In Alzheimer’s, too many connections are lost, affecting memory and thinking.
It raises the question: Could this same molecule that helps build the brain in infancy also help protect the brain later in life?
The research team is now studying whether IL34 might be used to reopen windows of brain flexibility to protect the brain as we age.
The study was funded in part by grants from the National Institutes of Health and the Cure Alzheimer’s Fund.