Transplanting human brain cells into mice makes the mice smarter, a new study shows.
But the smart-making brain cells are not the nerve cells most people think of as controlling thoughts. Instead, they are part of the supporting cast of brain cells known as glia (Greek for “glue”).
Scientists have long seen glia, including a subset known as astrocytes, as support cells that feed neurons, mop up excess neurotransmitters and generally help hold the brain together. The new study, published March 7 in Cell Stem Cell, shows that glial cells also influence memory formation and could change how scientists think the brain works, says R. Douglas Fields of the National Institute of Child Health and Human Development. “It’s a paradigm-shifting paper,” says Fields, who was not involved in the work.
In the new study, researchers led by neurologist and stem cell biologist Steven Goldman and neurobiologist Maiken Nedergaard of the University of Rochester Medical Center in New York implanted human cells called glial progenitor cells into the brains of newborn mice. Glial progenitor cells are a type of stem cell that is poised to make several varieties of glia, including astrocytes. Previously, the researchers had transplanted human glial progenitor cells into the brains of mice that had a genetic disorder mimicking multiple sclerosis. The glial progenitor cells healed the mice, allowing them to live a normal life span. That result held promise that such cell transplants might help people with neurological disorders.
The researchers also noticed something curious in the brains of mice that had received human cell transplants. “The shocker was that all the glial progenitors were human and had completely taken over the mouse progenitors,” Goldman says. The finding made the researchers wonder what effect human cells might have on otherwise normal mice.
Although many neuroscientists essentially ignore glia, it is becoming clear that the cells — which make up about 90 percent of the brain — are more important than some people believe. Astrocytes are required for nerve cells, or neurons, to make connections, called synapses, with each other. While neurons pretty much look and behave the same from species to species, human astrocytes are much larger and more complex than those from other species, leading some scientists to wonder whether the cells are at least partly responsible for the human brain’s computing power.
To find out, the Rochester researchers tested human glial progenitor cells in the brains of normal mice. By the time the mice were 6 months old, the human cells had pushed out the mouse progenitor cells and replaced many of the mouse astrocytes with human astrocytes. Some mice got a transplant of mouse glial progenitors instead of human cells to make sure any effect was due to the action of human cells and not to having extra brain cells.
Astrocytes use calcium to communicate. In lab dish tests, human astrocytes passed calcium signals three times faster than mouse astrocytes did. And the human astrocytes helped forge stronger synapses between mouse neurons than the mouse’s own astrocytes did.
The researchers also put mice through a battery of tests, probing the animals’ ability to learn mazes, distinguish new objects from old ones, and learn that a certain sound portends a mild electric shock. It took normal mice and mice with mouse cell transplants several tries to pick up on the association between the sound and the shock. Mice with human astrocytes “pretty much picked up the association immediately and got more fearful,” Goldman says.
Since the mice have their own neurons, the memory boost must have come from the human cells, the researchers conclude. While evidence points to the astrocytes as the source of the enhancement, the researchers can’t rule out that undeveloped progenitor cells might also contribute.
In any case, the results indicate that human cells not only aid in learning and memory, but do it better than their rodent counterparts do.
“It’s a stunning result. It provides the first unequivocal evidence that astrocytes may well have been one of the evolutionary drivers of human capabilities,” says Bruce Ransom, a neuroscientist at the University of Washington. “As completely outrageous as it sounds, I think the evidence is such now that we have to take that very seriously.”
