Robert F. Bukati / AP
A team from Stanford University has demonstrated a new method of reducing memory in rats.
A spinal fluid infusion from young rats inversely reverses memory loss commonly seen in older animals, the group reported in the journal This Month. Nature.
A growth factor found in fluids also improves memory, albeit slightly less, says Tony Weiss-Corey, a neuroscientist and senior author of the study.
“When we put the factor in rats, they are actually better able to perform a memory task where they have to remember something (a small electric shock),” says Wyss-Coray.
Maria Lehtinen, a neuroscientist at Harvard Medical School, says research into the treatment of Alzheimer’s disease and other age-related conditions indicates “a whole new era” that affects a person’s memory and thinking. Study.
To date, most efforts to treat Alzheimer’s have focused on eliminating the symptoms of the disease: the toxic plaques and tangles that build up in the brain. These efforts have produced drugs that can reduce plaque and tangles, but there is still much to be done to preserve a person’s thoughts and memories.
Recent findings on spinal fluid suggest that other treatments may help, even if they do not affect the underlying disease process.
“What we’re seeing is that there’s a lot more going on and aging creates a lot of abnormalities that contribute to cognitive decline and dementia,” says Wyss-Coray.
A balm for a forgotten rat
The new study involved older rats, who developed memory problems similar to those of their human counterparts.
For example, a painful experience will create a memory that lasts for weeks or even months in a young animal, says Weiss-Corey. As a result, animals will continue to freeze in response to a light or sound that was once accompanied by an electric shock.
“When they get older, they tend to forget about it,” he says. “After a few days they can’t remember that they were in a bad environment.”
Wyss-Coray’s lab has expressed surprise that one of the reasons for their memory fading is cerebrospinal fluid, or CSF, which bathes the brain and spinal cord. Brain cells depend on this fluid, and its structure changes dramatically as the animal ages.
But they did not test the concept because it is so difficult to get spinal fluid out of a small animal. This has changed, thanks to Tal Iram, a postdoctoral research fellow at the lab who was determined to overcome technical barriers.
A laborious process that took several months, Iram was able to collect enough spinal fluid from young rats to run an experiment that transmitted the fluid to older animals.
“We hoped that by mimicking a young environment, the brain would respond to it with greater efficiency,” Wyss-Coray said.
The old rats began to act like their little rivals when it came to recalling an experience. It was a remarkable result, but the team still needs to find out why the test worked.
So they conducted genetic tests that showed that the youngest spinal fluid response was found in some specialized cells in the hippocampus, an area that is important for memory.
These cells, known as oligodendrocytes, form myelin sheaths, which enclose the brain and are important for memory.
Further experiments have suggested that oligodendrocytes respond to an increase in spinal fluid called FGF17, which decreases with age.
Team success with FGF17 is important in improving memory because it can lead to a drug that can be mass-produced. But even with such drugs, scientists need to figure out how to safely deliver them to the human brain.
More reasons come
FGF17 is probably one of the many substances involved in brain aging, says Wyss-Coray. But in the case of rats, its effectiveness suggests that recovering one of these substances may make a difference.
An aging brain with memory loss is a lot like “an old car that broke down,” he says. “But like a car repair, you don’t have to fix all the parts, you have to find the key parts.”
At least some of it is found in spinal fluid, says Lehtinen.
His own lab is researching the role of cerebrospinal fluid in the development of the rat brain.
“We’ve found that CSF provides these important health and growth-promoting factors that can fundamentally improve brain growth,” he says. “What has been lacking so far is the next step in testing whether these CSF factors can benefit adults. [brains]”
New research suggests they could, he says.