You leave your car in a vast, crowded parking lot, and when you return, you have no idea where it is. The ensuing search is frustrating, time-consuming and a little embarrassing.
That experience occurs more frequently as we get older, because the functions of the part of the brain that encodes spatial and episodic memories — the hippocampus — decline with age.
But now neuroscientists at the Stanford University School of Medicine have shown that — in mice — an infusion of plasma taken from human umbilical cords improves the hippocampus's functioning, resulting in significant gains in memory and cognition needed for tasks such as finding a car in a full parking lot. They also isolated the protein, known as TIMP2, that they say is responsible for the improvements.
The research, published Wednesday in the journal Nature, could one day hold implications for the treatment of Alzheimer's disease and other conditions that erode memory and cognition.
“That TIMP2 protein might have some translational promise, some therapeutic promise, in humans,” said Joe Castellano, a postdoctoral researcher who identified the protein among scores of others in the blood.
TIMP2 appears to improve the transmission of information across gaps — known as synapses — between cells in the hippocampus, Castellano said. The quantity of the substance in the blood declines as people age.
“There seems to be something in young human blood that is not in old human blood that can reactivate and rejuvenate these old brains and make mice smarter again,” said Tony Wyss-Coray, a professor of neurology at Stanford who led the research team.
The researchers, however, voiced caution because most therapeutic approaches to disease that work in mice or other lab animals do not succeed in humans. And before it could be tried in humans, any substance would face years of safety testing.
But because the current study was conducted with human cord plasma, it is a big step forward, they said. “It’s not some random molecule that we found somewhere,” Wyss-Coray said. “It’s actually produced in humans.”
That raises the possibility of using TIMP2 to slow the aging of other tissue in the body, he said. Scientists don't actually know whether different organs age at the same rate and are not sure where the protein is produced. “Where does TIMP2 come from? Which organs produce it?” Wyss-Coray said. “And if it’s multiple organs, does it change with aging at the same speed, and can we interfere with that?”
The researchers had previously shown that they could improve learning and memory in older mice by injecting them with plasma taken from young mice.
In this study, the team injected the plasma — the liquid that remains when blood cells are removed — into older mice whose immune systems were weakened so that their natural defenses would not attack the proteins.
They could not send the rodents scurrying after tiny vehicles in a miniature parking lot. Instead, they tested them in a maze to determine how long it took the mice to find their way to a dark and confined space they consider secure, Castellano said. The older mice treated with human cord plasma regained about half their speed at finding the correct location, according to Wyss-Coray.
A second test that required the mice to recognize contextual cues to perform a task confirmed the gains, Castellano said.