A new study involving a missing molecule and some lucky mice suggests that rewiring the brain in adulthood isn’t just science fiction—it’s a distinct biological possibility.
We have long been told that the brain is a bit like drying cement: malleable and impressionable when we are young, but rigid and set in its ways once we hit adulthood. This biological dogma has been particularly discouraging for neurodevelopmental conditions like Down syndrome. The prevailing wisdom has been that if you want to fix the wiring, you have to get in there early—really early, like, before birth early.
But a team of researchers from the University of Virginia and the Salk Institute just threw a wrench—or rather, a protein—into that assumption.
In a study published this week in Cell Reports, scientists managed to “rewire” faulty brain circuits in adult mice with Down syndrome. They didn’t do it with invasive surgery or time travel. They did it by simply putting back a molecule that had gone missing.
The Case of the Missing Gardener
To understand what the researchers did, you have to meet the astrocyte. For a long time, these star-shaped brain cells were dismissed as mere “packing peanuts”—the glue that held the important neurons together. But in recent years, neuroscientists have realized that astrocytes are actually the brain’s gardeners. They prune connections, feed neurons, and generally keep the landscape tidy.
One of the tools these cellular gardeners use is a molecule called pleiotrophin. It’s essential for building synapses—the bridges that allow neurons to chat with one another.
“In Down syndrome, it looks like the gardeners are running low on supplies,” says Dr. Ashley Brandebura, a lead researcher on the study now at the University of Virginia School of Medicine. Her team found that in mice modeling Down syndrome, levels of pleiotrophin were surprisingly low. The result? A neural landscape that wasn’t quite connecting as it should.
A New Lease on Life (for Neurons)
Here is where the science gets cool. The team didn’t try to fix the brain while it was forming. They waited until the mice were fully grown adults. Using a modified virus—stripped of its ability to make you sick and repurposed as a delivery truck—they shipped a fresh supply of pleiotrophin directly to the astrocytes in the mice’s brains.
The results were striking. The astrocytes, seemingly re-energized by the supply drop, got back to work. They started building new synapses in the hippocampus, the brain’s command center for learning and memory.
More importantly, the brains showed improved plasticity. In neuroscience, plasticity is the holy grail; it’s the ability of the brain to change, adapt, and learn new tricks. Essentially, the researchers turned the “wet cement” sign back on.
Beyond the Mouse Cage
Now, before we get ahead of ourselves: These are mice, not humans. A mouse successfully navigating a maze is a long way from a clinical treatment for people. We are likely years, if not decades, away from a pharmacy-ready therapy.
However, the implications here are massive. This study serves as a proof-of-concept that the adult brain is not a lost cause. It challenges the heartbreaking notion that once a developmental window closes, it’s locked forever.
“This is really exciting because it suggests we can target astrocytes to rewire the brain circuitry at adult ages,” Dr. Brandebura noted.
The ripple effects could go far beyond Down syndrome. If we can figure out how to coax astrocytes into repairing wiring in adults, it could open doors for treating Alzheimer’s disease, Fragile X syndrome, and perhaps even traumatic brain injuries.
For now, the cement is still drying. But thanks to a missing molecule and some very persistent scientists, we now know it might be possible to add a little more water to the mix.
