If the results can be duplicated in humans, it could mean new therapeutic approaches for treating dementias such as Alzheimer’s disease.
For the study, published in the journal Nature Medicine, scientists evaluated the performance of older mice on standard lab tests of spatial memory after these mice had received infusions of plasma (the cell-free part of blood) from both young and old mice, or no plasma at all.
“This could have been done 20 years ago,” said senior author Tony Wyss-Coray, Ph.D., a professor of neurology and neurological sciences, who is also senior research career scientist at the Veterans Affairs Palo Alto Health Care System.
“You don’t need to know anything about how the brain works. You just give an old mouse young blood and see if the animal is smarter than before. It’s just that nobody did it.”
The researchers paid special attention to the hippocampus. In both mice and humans, this brain structure is critical for forming certain types of memories, particularly the recollection and recognition of spatial patterns.
“That’s what you need to use when, for example, you try to find your car in a parking lot or navigate around a city without using your GPS system,” Wyss-Coray said.
The hippocampus is especially vulnerable to the normal aging process, slowly wearing away as people age. In dementias such as Alzheimer’s disease, hippocampal deterioration is accelerated, leading to an inability to create new memories.
“We know that detrimental anatomical and functional changes occur in the hippocampus as mice and people get older,” said the study’s lead author, Saul Villeda, Ph.D. “This is just from natural aging. We’re all heading in that direction.”
When the researchers compared hippocampi from old mice whose circulatory systems had been conjoined with those of young mice to hippocampi from old mice that had been paired with other old mice, they found consistent differences in several biological measures known to be important for the encoding of new experiences.
The old mice infused with the blood of young mice made greater amounts of certain substances that hippocampal cells are known to produce when learning is taking place.
“There are factors present in blood from young mice that can recharge an old mouse’s brain so that it functions more like a younger one,” Wyss-Coray said. “We’re working intensively to find out what those factors might be and from exactly which tissues they originate.”
“We don’t know yet if this will work in humans,” he said, adding that he hopes to find out sooner rather than later. A near-term goal of his company is to test this proposition through a clinical trial.